Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

Toni I. Pollin, Tamara Isakova, Kathleen A. Jablonski, Paul I W de Bakker, Andrew Taylor, Jarred McAteer, Qing Pan, Edward S. Horton, Linda M. Delahanty, David Altshuler, Alan R. Shuldiner, Ronald B. Goldberg, Jose C. Florez, Paul W. Franks, George A. Bray, Iris W. Culbert, Catherine M. Champagne, Barbara Eberhardt, Frank Greenway, Fonda G. GuilloryApril A. Herbert, Michael L. Jeffirs, Betty M. Kennedy, Jennifer C. Lovejoy, Laura H. Morris, Lee E. Melancon, Donna Ryan, Deborah A. Sanford, Kenneth G. Smith, Lisa L. Smith, Julia A. St. Amant, Richard T. Tulley, Paula C. Vicknair, Donald Williamson, Jeffery J. Zachwieja, Kenneth S. Polonsky, Janet Tobian, David Ehrmann, Margaret J. Matulik, Bart Clark, Kirsten Czech, Catherine DeSandre, Ruthanne Hilbrich, Wylie McNabb, Ann R. Semenske, Jose F. Caro, Pamela G. Watson, Barry J. Goldstein, Kellie A. Smith, Jewel Mendoza, Renee Liberoni, Constance Pepe, John Spandorfer, Richard P. Donahue, Ronald B. Goldberg, Ronald Prineas, Patricia Rowe, Jeanette Calles, Paul Cassanova-Romero, Hermes J. Florez, Anna Giannella, Lascelles Kirby, Carmen Larreal, Valerie McLymont, Jadell Mendez, Juliet Ojito, Arlette Perry, Patrice Saab, Steven M. Haffner, Maria G. Montez, Carlos Lorenzo, Arlene Martinez, Richard F. Hamman, Patricia V. Nash, Lisa Testaverde, Denise R. Anderson, Larry B. Ballonoff, Alexis Bouffard, B. Ned Calonge, Lynne Delve, Martha Farago, James O. Hill, Shelley R. Hoyer, Bonnie T. Jortberg, Dione Lenz, Marsha Miller, David W. Price, Judith G. Regensteiner, Helen Seagle, Carissa M. Smith, Sheila C. Steinke, Brent VanDorsten, Edward S. Horton, Kathleen E. Lawton, Ronald A. Arky, Marybeth Bryant, Jacqueline P. Burke, Enrique Caballero, Karen M. Callaphan, Om P. Ganda, Therese Franklin, Sharon D. Jackson, Alan M. Jacobsen, Alan M. Jacobsen, Lyn M. Kula, Margaret Kocal, Maureen A. Malloy, Maryanne Nicosia, Cathryn F. Oldmixon, Jocelyn Pan, Marizel Quitingon, Stacy Rubtchinsky, Ellen W. Seely, Dana Schweizer, Donald Simonson, Fannie Smith, Caren G. Solomon, James Warram, Steven E. Kahn, Brenda K. Montgomery, Wilfred Fujimoto, Robert H. Knopp, Edward W. Lipkin, Michelle Marr, Dace Trence, Abbas E. Kitabchi, Mary E. Murphy, William B. Applegate, Michael Bryer-Ash, Sandra L. Frieson, Raed Imseis, Helen Lambeth, Lynne C. Lichtermann, Hooman Oktaei, Lily M K Rutledge, Amy R. Sherman, Clara M. Smith, Judith E. Soberman, Beverly Williams-Cleaves, Boyd E. Metzger, Mariana K. Johnson, Catherine Behrends, Michelle Cook, Marian Fitzgibbon, Mimi M. Giles, Deloris Heard, Cheryl K H Johnson, Diane Larsen, Anne Lowe, Megan Lyman, David McPherson, Mark E. Molitch, Thomas Pitts, Renee Reinhart, Susan Roston, Pamela A. Schinleber, David M. Nathan, Charles McKitrick, Heather Turgeon, Kathy Abbott, Ellen Anderson, Laurie Bissett, Enrico Cagliero, Jose C. Florez, Linda Delahanty, Valerie Goldman, Alexandra Poulos, Jerrold M. Olefsky, Mary Lou Carrion-Petersen, Elizabeth Barrett-Connor, Steven V. Edelman, Robert R. Henry, Javiva Horne, Simona Szerdi Janesch, Diana Leos, Sundar Mudaliar, William Polonsky, Jean Smith, Karen Vejvoda, F. Xavier Pi-Sunyer, Jane E. Lee, David B. Allison, Nancy J. Aronoff, Jill P. Crandall, Sandra T. Foo, Carmen Pal, Kathy Parkes, Mary Beth Pena, Ellen S. Rooney, Gretchen E H van Wye, Kristine A. Viscovich, David Marrero, Melvin J. Prince, Susie M. Kelly, Yolanda F. Dotson, Edwin S. Fineberg, John C. Guare, Angela M. Hadden, James M. Ignaut, Marcia L. Jackson, Marion S. Kirkman, Kieren Mather, Beverly D. Porter, Paris Roach, Nancy D. Rowland, Madelyn L. Wheeler, Robert E. Ratner, Gretchen Youssef, Sue Shapiro, Catherine Bavido-Arrage, Geraldine Boggs, Marjorie Bronsord, Ernestine Brown, Wayman W. Cheatham, Susan Cola, Cindy Evans, Peggy Gibbs, Tracy Kellum, Claresa Levatan, Asha K. Nair, Maureen Passaro, Gabriel Uwaifo, Mohammed F. Saad, Maria Budget, Sujata Jinagouda, Khan Akbar, Claudia Conzues, Perpetua Magpuri, Kathy Ngo, Amer Rassam, Debra Waters, Kathy Xapthalamous, Julio V. Santiago, Samuel Dagogo-Jack, Neil H. White, Samia Das, Ana Santiago, Angela Brown, Edwin Fisher, Emma Hurt, Tracy Jones, Michelle Kerr, Lucy Ryder, Cormarie Wernimont, Christopher D. Saudek, Vanessa Bradley, Emily Sullivan, Tracy Whittington, Caroline Abbas, Frederick L. Brancati, Jeanne M. Clark, Jeanne B. Charleston, Janice Freel, Katherine Horak, Dawn Jiggetts, Deloris Johnson, Hope Joseph, Kimberly Loman, Henry Mosley, Richard R. Rubin, Alafia Samuels, Kerry J. Stewart, Paula Williamson, David S. Schade, Karwyn S. Adams, Carolyn Johannes, Leslie F. Atler, Patrick J. Boyle, Mark R. Burge, Janene L. Canady, Lisa Chai, Ysela Gonzales, Doris A. Hernandez-McGinnis, Patricia Katz, Carolyn King, Amer Rassam, Sofya Rubinchik, Willette Senter, Debra Waters, Harry Shamoon, Janet O. Brown, Elsie Adorno, Liane Cox, Jill Crandall, Helena Duffy, Samuel Engel, Allison Friedler, Crystal J. Howard-Century, Stacey Kloiber, Nadege Longchamp, Helen Martinez, Dorothy Pompi, Jonathan Scheindlin, Elissa Violino, Elizabeth Walker, Judith Wylie-Rosett, Elise Zimmerman, Joel Zonszein, Trevor Orchard, Rena R. Wing, Gaye Koenning, M. Kaye Kramer, Susan Barr, Miriam Boraz, Lisa Clifford, Rebecca Culyba, Marlene Frazier, Ryan Gilligan, Susan Harrier, Louann Harris, Susan Jeffries, Andrea Kriska, Qurashia Manjoo, Monica Mullen, Alicia Noel, Amy Otto, Linda Semler, Cheryl F. Smith, Marie Smith, Elizabeth Venditti, Valarie Weinzierl, Katherine V. Williams, Tara Wilson, Richard F. Arakaki, Renee W. Latimer, Narleen K. Baker-Ladao, Ralph Beddow, Lorna Dias, Jillian Inouye, Marjorie K. Mau, Kathy Mikami, Pharis Mohideen, Sharon K. Odom, Raynette U. Perry, William C. Knowler, Norman Cooeyate, Mary A. Hoskin, Carol A. Percy, Kelly J. Acton, Vickie L. Andre, Rosalyn Barber, Shandiin Begay, Peter H. Bennett, Mary Beth Benson, Evelyn C. Bird, Brenda A. Broussard, Marcella Chavez, Tara Dacawyma, Matthew S. Doughty, Roberta Duncan, Cyndy Edgerton, Jacqueline M. Ghahate, Justin Glass, Martia Glass, Dorothy Gohdes, Wendy Grant, Robert L. Hanson, Ellie Horse, Louise E. Ingraham, Merry Jackson, Priscilla Jay, Roylen S. Kaskalla, David Kessler, Kathleen M. Kobus, Jonathan Krakoff, Catherine Manus, Sara Michaels, Tina Morgan, Yolanda Nashboo, Julie A. Nelson, Steven Poirier, Evette Polczynski, Mike Reidy, Jeanine Roumain, Debra Rowse, Sandra Sangster, Janet Sewenemewa, Darryl Tonemah, Charlton Wilson, Michelle Yazzie, Raymond Bain, Sarah Fowler, Tina Brenneman, Solome Abebe, Julie Bamdad, Jackie Callaghan, Sharon L. Edelstein, Yuping Gao, Kristina L. Grimes, Nisha Grover, Lori Haffner, Steve Jones, Tara L. Jones, Richard Katz, John M. Lachin, Pamela Mucik, Robert Orlosky, James Rochon, Alla Sapozhnikova, Hanna Sherif, Charlotte Stimpson, Marinella Temprosa, Fredricka Walker-Murray, Santica Marcovina, Greg Strylewicz, F. Alan Aldrich, Dan O'Leary, Elizabeth Stamm, Pentti Rautaharju, Ronald J. Prineas, Teresa Alexander, Charles Campbell, Sharon Hall, Yabing Li, Margaret Mills, Nancy Pemberton, Farida Rautaharju, Zhuming Zhang, Elizabeth Mayer-Davis, Robert R. Moran, Ted Ganiats, Kristin David, Andrew J. Sarkin, R. Eastman, Judith Fradkin, Sanford Garfield, Edward Gregg, Ping Zhang, William Herman, Jose C. Florez, David Altshuler, Paul I W de Bakker, Paul W. Franks, Robert L. Hanson, Kathleen Jablonski, William C. Knowler, Jarred B. McAteer, Toni I. Pollin, Alan R. Shuldiner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

Original languageEnglish
Article numbere1002895
JournalPLoS Genetics
Volume8
Issue number8
DOIs
StatePublished - Aug 2012

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metformin
diabetes
Metformin
lifestyle
Life Style
allele
lipid
Alleles
alleles
Lipids
lipids
pipes
Therapeutics
placebos
Weight Loss
weight loss
pipe
Placebos
fasting
physical activity

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Pollin, T. I., Isakova, T., Jablonski, K. A., de Bakker, P. I. W., Taylor, A., McAteer, J., ... Shuldiner, A. R. (2012). Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program. PLoS Genetics, 8(8), [e1002895]. https://doi.org/10.1371/journal.pgen.1002895

Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment : The Diabetes Prevention Program. / Pollin, Toni I.; Isakova, Tamara; Jablonski, Kathleen A.; de Bakker, Paul I W; Taylor, Andrew; McAteer, Jarred; Pan, Qing; Horton, Edward S.; Delahanty, Linda M.; Altshuler, David; Shuldiner, Alan R.; Goldberg, Ronald B.; Florez, Jose C.; Franks, Paul W.; Bray, George A.; Culbert, Iris W.; Champagne, Catherine M.; Eberhardt, Barbara; Greenway, Frank; Guillory, Fonda G.; Herbert, April A.; Jeffirs, Michael L.; Kennedy, Betty M.; Lovejoy, Jennifer C.; Morris, Laura H.; Melancon, Lee E.; Ryan, Donna; Sanford, Deborah A.; Smith, Kenneth G.; Smith, Lisa L.; St. Amant, Julia A.; Tulley, Richard T.; Vicknair, Paula C.; Williamson, Donald; Zachwieja, Jeffery J.; Polonsky, Kenneth S.; Tobian, Janet; Ehrmann, David; Matulik, Margaret J.; Clark, Bart; Czech, Kirsten; DeSandre, Catherine; Hilbrich, Ruthanne; McNabb, Wylie; Semenske, Ann R.; Caro, Jose F.; Watson, Pamela G.; Goldstein, Barry J.; Smith, Kellie A.; Mendoza, Jewel; Liberoni, Renee; Pepe, Constance; Spandorfer, John; Donahue, Richard P.; Goldberg, Ronald B.; Prineas, Ronald; Rowe, Patricia; Calles, Jeanette; Cassanova-Romero, Paul; Florez, Hermes J.; Giannella, Anna; Kirby, Lascelles; Larreal, Carmen; McLymont, Valerie; Mendez, Jadell; Ojito, Juliet; Perry, Arlette; Saab, Patrice; Haffner, Steven M.; Montez, Maria G.; Lorenzo, Carlos; Martinez, Arlene; Hamman, Richard F.; Nash, Patricia V.; Testaverde, Lisa; Anderson, Denise R.; Ballonoff, Larry B.; Bouffard, Alexis; Calonge, B. Ned; Delve, Lynne; Farago, Martha; Hill, James O.; Hoyer, Shelley R.; Jortberg, Bonnie T.; Lenz, Dione; Miller, Marsha; Price, David W.; Regensteiner, Judith G.; Seagle, Helen; Smith, Carissa M.; Steinke, Sheila C.; VanDorsten, Brent; Horton, Edward S.; Lawton, Kathleen E.; Arky, Ronald A.; Bryant, Marybeth; Burke, Jacqueline P.; Caballero, Enrique; Callaphan, Karen M.; Ganda, Om P.; Franklin, Therese; Jackson, Sharon D.; Jacobsen, Alan M.; Jacobsen, Alan M.; Kula, Lyn M.; Kocal, Margaret; Malloy, Maureen A.; Nicosia, Maryanne; Oldmixon, Cathryn F.; Pan, Jocelyn; Quitingon, Marizel; Rubtchinsky, Stacy; Seely, Ellen W.; Schweizer, Dana; Simonson, Donald; Smith, Fannie; Solomon, Caren G.; Warram, James; Kahn, Steven E.; Montgomery, Brenda K.; Fujimoto, Wilfred; Knopp, Robert H.; Lipkin, Edward W.; Marr, Michelle; Trence, Dace; Kitabchi, Abbas E.; Murphy, Mary E.; Applegate, William B.; Bryer-Ash, Michael; Frieson, Sandra L.; Imseis, Raed; Lambeth, Helen; Lichtermann, Lynne C.; Oktaei, Hooman; Rutledge, Lily M K; Sherman, Amy R.; Smith, Clara M.; Soberman, Judith E.; Williams-Cleaves, Beverly; Metzger, Boyd E.; Johnson, Mariana K.; Behrends, Catherine; Cook, Michelle; Fitzgibbon, Marian; Giles, Mimi M.; Heard, Deloris; Johnson, Cheryl K H; Larsen, Diane; Lowe, Anne; Lyman, Megan; McPherson, David; Molitch, Mark E.; Pitts, Thomas; Reinhart, Renee; Roston, Susan; Schinleber, Pamela A.; Nathan, David M.; McKitrick, Charles; Turgeon, Heather; Abbott, Kathy; Anderson, Ellen; Bissett, Laurie; Cagliero, Enrico; Florez, Jose C.; Delahanty, Linda; Goldman, Valerie; Poulos, Alexandra; Olefsky, Jerrold M.; Carrion-Petersen, Mary Lou; Barrett-Connor, Elizabeth; Edelman, Steven V.; Henry, Robert R.; Horne, Javiva; Janesch, Simona Szerdi; Leos, Diana; Mudaliar, Sundar; Polonsky, William; Smith, Jean; Vejvoda, Karen; Pi-Sunyer, F. Xavier; Lee, Jane E.; Allison, David B.; Aronoff, Nancy J.; Crandall, Jill P.; Foo, Sandra T.; Pal, Carmen; Parkes, Kathy; Pena, Mary Beth; Rooney, Ellen S.; van Wye, Gretchen E H; Viscovich, Kristine A.; Marrero, David; Prince, Melvin J.; Kelly, Susie M.; Dotson, Yolanda F.; Fineberg, Edwin S.; Guare, John C.; Hadden, Angela M.; Ignaut, James M.; Jackson, Marcia L.; Kirkman, Marion S.; Mather, Kieren; Porter, Beverly D.; Roach, Paris; Rowland, Nancy D.; Wheeler, Madelyn L.; Ratner, Robert E.; Youssef, Gretchen; Shapiro, Sue; Bavido-Arrage, Catherine; Boggs, Geraldine; Bronsord, Marjorie; Brown, Ernestine; Cheatham, Wayman W.; Cola, Susan; Evans, Cindy; Gibbs, Peggy; Kellum, Tracy; Levatan, Claresa; Nair, Asha K.; Passaro, Maureen; Uwaifo, Gabriel; Saad, Mohammed F.; Budget, Maria; Jinagouda, Sujata; Akbar, Khan; Conzues, Claudia; Magpuri, Perpetua; Ngo, Kathy; Rassam, Amer; Waters, Debra; Xapthalamous, Kathy; Santiago, Julio V.; Dagogo-Jack, Samuel; White, Neil H.; Das, Samia; Santiago, Ana; Brown, Angela; Fisher, Edwin; Hurt, Emma; Jones, Tracy; Kerr, Michelle; Ryder, Lucy; Wernimont, Cormarie; Saudek, Christopher D.; Bradley, Vanessa; Sullivan, Emily; Whittington, Tracy; Abbas, Caroline; Brancati, Frederick L.; Clark, Jeanne M.; Charleston, Jeanne B.; Freel, Janice; Horak, Katherine; Jiggetts, Dawn; Johnson, Deloris; Joseph, Hope; Loman, Kimberly; Mosley, Henry; Rubin, Richard R.; Samuels, Alafia; Stewart, Kerry J.; Williamson, Paula; Schade, David S.; Adams, Karwyn S.; Johannes, Carolyn; Atler, Leslie F.; Boyle, Patrick J.; Burge, Mark R.; Canady, Janene L.; Chai, Lisa; Gonzales, Ysela; Hernandez-McGinnis, Doris A.; Katz, Patricia; King, Carolyn; Rassam, Amer; Rubinchik, Sofya; Senter, Willette; Waters, Debra; Shamoon, Harry; Brown, Janet O.; Adorno, Elsie; Cox, Liane; Crandall, Jill; Duffy, Helena; Engel, Samuel; Friedler, Allison; Howard-Century, Crystal J.; Kloiber, Stacey; Longchamp, Nadege; Martinez, Helen; Pompi, Dorothy; Scheindlin, Jonathan; Violino, Elissa; Walker, Elizabeth; Wylie-Rosett, Judith; Zimmerman, Elise; Zonszein, Joel; Orchard, Trevor; Wing, Rena R.; Koenning, Gaye; Kramer, M. Kaye; Barr, Susan; Boraz, Miriam; Clifford, Lisa; Culyba, Rebecca; Frazier, Marlene; Gilligan, Ryan; Harrier, Susan; Harris, Louann; Jeffries, Susan; Kriska, Andrea; Manjoo, Qurashia; Mullen, Monica; Noel, Alicia; Otto, Amy; Semler, Linda; Smith, Cheryl F.; Smith, Marie; Venditti, Elizabeth; Weinzierl, Valarie; Williams, Katherine V.; Wilson, Tara; Arakaki, Richard F.; Latimer, Renee W.; Baker-Ladao, Narleen K.; Beddow, Ralph; Dias, Lorna; Inouye, Jillian; Mau, Marjorie K.; Mikami, Kathy; Mohideen, Pharis; Odom, Sharon K.; Perry, Raynette U.; Knowler, William C.; Cooeyate, Norman; Hoskin, Mary A.; Percy, Carol A.; Acton, Kelly J.; Andre, Vickie L.; Barber, Rosalyn; Begay, Shandiin; Bennett, Peter H.; Benson, Mary Beth; Bird, Evelyn C.; Broussard, Brenda A.; Chavez, Marcella; Dacawyma, Tara; Doughty, Matthew S.; Duncan, Roberta; Edgerton, Cyndy; Ghahate, Jacqueline M.; Glass, Justin; Glass, Martia; Gohdes, Dorothy; Grant, Wendy; Hanson, Robert L.; Horse, Ellie; Ingraham, Louise E.; Jackson, Merry; Jay, Priscilla; Kaskalla, Roylen S.; Kessler, David; Kobus, Kathleen M.; Krakoff, Jonathan; Manus, Catherine; Michaels, Sara; Morgan, Tina; Nashboo, Yolanda; Nelson, Julie A.; Poirier, Steven; Polczynski, Evette; Reidy, Mike; Roumain, Jeanine; Rowse, Debra; Sangster, Sandra; Sewenemewa, Janet; Tonemah, Darryl; Wilson, Charlton; Yazzie, Michelle; Bain, Raymond; Fowler, Sarah; Brenneman, Tina; Abebe, Solome; Bamdad, Julie; Callaghan, Jackie; Edelstein, Sharon L.; Gao, Yuping; Grimes, Kristina L.; Grover, Nisha; Haffner, Lori; Jones, Steve; Jones, Tara L.; Katz, Richard; Lachin, John M.; Mucik, Pamela; Orlosky, Robert; Rochon, James; Sapozhnikova, Alla; Sherif, Hanna; Stimpson, Charlotte; Temprosa, Marinella; Walker-Murray, Fredricka; Marcovina, Santica; Strylewicz, Greg; Aldrich, F. Alan; O'Leary, Dan; Stamm, Elizabeth; Rautaharju, Pentti; Prineas, Ronald J.; Alexander, Teresa; Campbell, Charles; Hall, Sharon; Li, Yabing; Mills, Margaret; Pemberton, Nancy; Rautaharju, Farida; Zhang, Zhuming; Mayer-Davis, Elizabeth; Moran, Robert R.; Ganiats, Ted; David, Kristin; Sarkin, Andrew J.; Eastman, R.; Fradkin, Judith; Garfield, Sanford; Gregg, Edward; Zhang, Ping; Herman, William; Florez, Jose C.; Altshuler, David; de Bakker, Paul I W; Franks, Paul W.; Hanson, Robert L.; Jablonski, Kathleen; Knowler, William C.; McAteer, Jarred B.; Pollin, Toni I.; Shuldiner, Alan R.

In: PLoS Genetics, Vol. 8, No. 8, e1002895, 08.2012.

Research output: Contribution to journalArticle

Pollin, TI, Isakova, T, Jablonski, KA, de Bakker, PIW, Taylor, A, McAteer, J, Pan, Q, Horton, ES, Delahanty, LM, Altshuler, D, Shuldiner, AR, Goldberg, RB, Florez, JC, Franks, PW, Bray, GA, Culbert, IW, Champagne, CM, Eberhardt, B, Greenway, F, Guillory, FG, Herbert, AA, Jeffirs, ML, Kennedy, BM, Lovejoy, JC, Morris, LH, Melancon, LE, Ryan, D, Sanford, DA, Smith, KG, Smith, LL, St. Amant, JA, Tulley, RT, Vicknair, PC, Williamson, D, Zachwieja, JJ, Polonsky, KS, Tobian, J, Ehrmann, D, Matulik, MJ, Clark, B, Czech, K, DeSandre, C, Hilbrich, R, McNabb, W, Semenske, AR, Caro, JF, Watson, PG, Goldstein, BJ, Smith, KA, Mendoza, J, Liberoni, R, Pepe, C, Spandorfer, J, Donahue, RP, Goldberg, RB, Prineas, R, Rowe, P, Calles, J, Cassanova-Romero, P, Florez, HJ, Giannella, A, Kirby, L, Larreal, C, McLymont, V, Mendez, J, Ojito, J, Perry, A, Saab, P, Haffner, SM, Montez, MG, Lorenzo, C, Martinez, A, Hamman, RF, Nash, PV, Testaverde, L, Anderson, DR, Ballonoff, LB, Bouffard, A, Calonge, BN, Delve, L, Farago, M, Hill, JO, Hoyer, SR, Jortberg, BT, Lenz, D, Miller, M, Price, DW, Regensteiner, JG, Seagle, H, Smith, CM, Steinke, SC, VanDorsten, B, Horton, ES, Lawton, KE, Arky, RA, Bryant, M, Burke, JP, Caballero, E, Callaphan, KM, Ganda, OP, Franklin, T, Jackson, SD, Jacobsen, AM, Jacobsen, AM, Kula, LM, Kocal, M, Malloy, MA, Nicosia, M, Oldmixon, CF, Pan, J, Quitingon, M, Rubtchinsky, S, Seely, EW, Schweizer, D, Simonson, D, Smith, F, Solomon, CG, Warram, J, Kahn, SE, Montgomery, BK, Fujimoto, W, Knopp, RH, Lipkin, EW, Marr, M, Trence, D, Kitabchi, AE, Murphy, ME, Applegate, WB, Bryer-Ash, M, Frieson, SL, Imseis, R, Lambeth, H, Lichtermann, LC, Oktaei, H, Rutledge, LMK, Sherman, AR, Smith, CM, Soberman, JE, Williams-Cleaves, B, Metzger, BE, Johnson, MK, Behrends, C, Cook, M, Fitzgibbon, M, Giles, MM, Heard, D, Johnson, CKH, Larsen, D, Lowe, A, Lyman, M, McPherson, D, Molitch, ME, Pitts, T, Reinhart, R, Roston, S, Schinleber, PA, Nathan, DM, McKitrick, C, Turgeon, H, Abbott, K, Anderson, E, Bissett, L, Cagliero, E, Florez, JC, Delahanty, L, Goldman, V, Poulos, A, Olefsky, JM, Carrion-Petersen, ML, Barrett-Connor, E, Edelman, SV, Henry, RR, Horne, J, Janesch, SS, Leos, D, Mudaliar, S, Polonsky, W, Smith, J, Vejvoda, K, Pi-Sunyer, FX, Lee, JE, Allison, DB, Aronoff, NJ, Crandall, JP, Foo, ST, Pal, C, Parkes, K, Pena, MB, Rooney, ES, van Wye, GEH, Viscovich, KA, Marrero, D, Prince, MJ, Kelly, SM, Dotson, YF, Fineberg, ES, Guare, JC, Hadden, AM, Ignaut, JM, Jackson, ML, Kirkman, MS, Mather, K, Porter, BD, Roach, P, Rowland, ND, Wheeler, ML, Ratner, RE, Youssef, G, Shapiro, S, Bavido-Arrage, C, Boggs, G, Bronsord, M, Brown, E, Cheatham, WW, Cola, S, Evans, C, Gibbs, P, Kellum, T, Levatan, C, Nair, AK, Passaro, M, Uwaifo, G, Saad, MF, Budget, M, Jinagouda, S, Akbar, K, Conzues, C, Magpuri, P, Ngo, K, Rassam, A, Waters, D, Xapthalamous, K, Santiago, JV, Dagogo-Jack, S, White, NH, Das, S, Santiago, A, Brown, A, Fisher, E, Hurt, E, Jones, T, Kerr, M, Ryder, L, Wernimont, C, Saudek, CD, Bradley, V, Sullivan, E, Whittington, T, Abbas, C, Brancati, FL, Clark, JM, Charleston, JB, Freel, J, Horak, K, Jiggetts, D, Johnson, D, Joseph, H, Loman, K, Mosley, H, Rubin, RR, Samuels, A, Stewart, KJ, Williamson, P, Schade, DS, Adams, KS, Johannes, C, Atler, LF, Boyle, PJ, Burge, MR, Canady, JL, Chai, L, Gonzales, Y, Hernandez-McGinnis, DA, Katz, P, King, C, Rassam, A, Rubinchik, S, Senter, W, Waters, D, Shamoon, H, Brown, JO, Adorno, E, Cox, L, Crandall, J, Duffy, H, Engel, S, Friedler, A, Howard-Century, CJ, Kloiber, S, Longchamp, N, Martinez, H, Pompi, D, Scheindlin, J, Violino, E, Walker, E, Wylie-Rosett, J, Zimmerman, E, Zonszein, J, Orchard, T, Wing, RR, Koenning, G, Kramer, MK, Barr, S, Boraz, M, Clifford, L, Culyba, R, Frazier, M, Gilligan, R, Harrier, S, Harris, L, Jeffries, S, Kriska, A, Manjoo, Q, Mullen, M, Noel, A, Otto, A, Semler, L, Smith, CF, Smith, M, Venditti, E, Weinzierl, V, Williams, KV, Wilson, T, Arakaki, RF, Latimer, RW, Baker-Ladao, NK, Beddow, R, Dias, L, Inouye, J, Mau, MK, Mikami, K, Mohideen, P, Odom, SK, Perry, RU, Knowler, WC, Cooeyate, N, Hoskin, MA, Percy, CA, Acton, KJ, Andre, VL, Barber, R, Begay, S, Bennett, PH, Benson, MB, Bird, EC, Broussard, BA, Chavez, M, Dacawyma, T, Doughty, MS, Duncan, R, Edgerton, C, Ghahate, JM, Glass, J, Glass, M, Gohdes, D, Grant, W, Hanson, RL, Horse, E, Ingraham, LE, Jackson, M, Jay, P, Kaskalla, RS, Kessler, D, Kobus, KM, Krakoff, J, Manus, C, Michaels, S, Morgan, T, Nashboo, Y, Nelson, JA, Poirier, S, Polczynski, E, Reidy, M, Roumain, J, Rowse, D, Sangster, S, Sewenemewa, J, Tonemah, D, Wilson, C, Yazzie, M, Bain, R, Fowler, S, Brenneman, T, Abebe, S, Bamdad, J, Callaghan, J, Edelstein, SL, Gao, Y, Grimes, KL, Grover, N, Haffner, L, Jones, S, Jones, TL, Katz, R, Lachin, JM, Mucik, P, Orlosky, R, Rochon, J, Sapozhnikova, A, Sherif, H, Stimpson, C, Temprosa, M, Walker-Murray, F, Marcovina, S, Strylewicz, G, Aldrich, FA, O'Leary, D, Stamm, E, Rautaharju, P, Prineas, RJ, Alexander, T, Campbell, C, Hall, S, Li, Y, Mills, M, Pemberton, N, Rautaharju, F, Zhang, Z, Mayer-Davis, E, Moran, RR, Ganiats, T, David, K, Sarkin, AJ, Eastman, R, Fradkin, J, Garfield, S, Gregg, E, Zhang, P, Herman, W, Florez, JC, Altshuler, D, de Bakker, PIW, Franks, PW, Hanson, RL, Jablonski, K, Knowler, WC, McAteer, JB, Pollin, TI & Shuldiner, AR 2012, 'Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program', PLoS Genetics, vol. 8, no. 8, e1002895. https://doi.org/10.1371/journal.pgen.1002895
Pollin, Toni I. ; Isakova, Tamara ; Jablonski, Kathleen A. ; de Bakker, Paul I W ; Taylor, Andrew ; McAteer, Jarred ; Pan, Qing ; Horton, Edward S. ; Delahanty, Linda M. ; Altshuler, David ; Shuldiner, Alan R. ; Goldberg, Ronald B. ; Florez, Jose C. ; Franks, Paul W. ; Bray, George A. ; Culbert, Iris W. ; Champagne, Catherine M. ; Eberhardt, Barbara ; Greenway, Frank ; Guillory, Fonda G. ; Herbert, April A. ; Jeffirs, Michael L. ; Kennedy, Betty M. ; Lovejoy, Jennifer C. ; Morris, Laura H. ; Melancon, Lee E. ; Ryan, Donna ; Sanford, Deborah A. ; Smith, Kenneth G. ; Smith, Lisa L. ; St. Amant, Julia A. ; Tulley, Richard T. ; Vicknair, Paula C. ; Williamson, Donald ; Zachwieja, Jeffery J. ; Polonsky, Kenneth S. ; Tobian, Janet ; Ehrmann, David ; Matulik, Margaret J. ; Clark, Bart ; Czech, Kirsten ; DeSandre, Catherine ; Hilbrich, Ruthanne ; McNabb, Wylie ; Semenske, Ann R. ; Caro, Jose F. ; Watson, Pamela G. ; Goldstein, Barry J. ; Smith, Kellie A. ; Mendoza, Jewel ; Liberoni, Renee ; Pepe, Constance ; Spandorfer, John ; Donahue, Richard P. ; Goldberg, Ronald B. ; Prineas, Ronald ; Rowe, Patricia ; Calles, Jeanette ; Cassanova-Romero, Paul ; Florez, Hermes J. ; Giannella, Anna ; Kirby, Lascelles ; Larreal, Carmen ; McLymont, Valerie ; Mendez, Jadell ; Ojito, Juliet ; Perry, Arlette ; Saab, Patrice ; Haffner, Steven M. ; Montez, Maria G. ; Lorenzo, Carlos ; Martinez, Arlene ; Hamman, Richard F. ; Nash, Patricia V. ; Testaverde, Lisa ; Anderson, Denise R. ; Ballonoff, Larry B. ; Bouffard, Alexis ; Calonge, B. Ned ; Delve, Lynne ; Farago, Martha ; Hill, James O. ; Hoyer, Shelley R. ; Jortberg, Bonnie T. ; Lenz, Dione ; Miller, Marsha ; Price, David W. ; Regensteiner, Judith G. ; Seagle, Helen ; Smith, Carissa M. ; Steinke, Sheila C. ; VanDorsten, Brent ; Horton, Edward S. ; Lawton, Kathleen E. ; Arky, Ronald A. ; Bryant, Marybeth ; Burke, Jacqueline P. ; Caballero, Enrique ; Callaphan, Karen M. ; Ganda, Om P. ; Franklin, Therese ; Jackson, Sharon D. ; Jacobsen, Alan M. ; Jacobsen, Alan M. ; Kula, Lyn M. ; Kocal, Margaret ; Malloy, Maureen A. ; Nicosia, Maryanne ; Oldmixon, Cathryn F. ; Pan, Jocelyn ; Quitingon, Marizel ; Rubtchinsky, Stacy ; Seely, Ellen W. ; Schweizer, Dana ; Simonson, Donald ; Smith, Fannie ; Solomon, Caren G. ; Warram, James ; Kahn, Steven E. ; Montgomery, Brenda K. ; Fujimoto, Wilfred ; Knopp, Robert H. ; Lipkin, Edward W. ; Marr, Michelle ; Trence, Dace ; Kitabchi, Abbas E. ; Murphy, Mary E. ; Applegate, William B. ; Bryer-Ash, Michael ; Frieson, Sandra L. ; Imseis, Raed ; Lambeth, Helen ; Lichtermann, Lynne C. ; Oktaei, Hooman ; Rutledge, Lily M K ; Sherman, Amy R. ; Smith, Clara M. ; Soberman, Judith E. ; Williams-Cleaves, Beverly ; Metzger, Boyd E. ; Johnson, Mariana K. ; Behrends, Catherine ; Cook, Michelle ; Fitzgibbon, Marian ; Giles, Mimi M. ; Heard, Deloris ; Johnson, Cheryl K H ; Larsen, Diane ; Lowe, Anne ; Lyman, Megan ; McPherson, David ; Molitch, Mark E. ; Pitts, Thomas ; Reinhart, Renee ; Roston, Susan ; Schinleber, Pamela A. ; Nathan, David M. ; McKitrick, Charles ; Turgeon, Heather ; Abbott, Kathy ; Anderson, Ellen ; Bissett, Laurie ; Cagliero, Enrico ; Florez, Jose C. ; Delahanty, Linda ; Goldman, Valerie ; Poulos, Alexandra ; Olefsky, Jerrold M. ; Carrion-Petersen, Mary Lou ; Barrett-Connor, Elizabeth ; Edelman, Steven V. ; Henry, Robert R. ; Horne, Javiva ; Janesch, Simona Szerdi ; Leos, Diana ; Mudaliar, Sundar ; Polonsky, William ; Smith, Jean ; Vejvoda, Karen ; Pi-Sunyer, F. Xavier ; Lee, Jane E. ; Allison, David B. ; Aronoff, Nancy J. ; Crandall, Jill P. ; Foo, Sandra T. ; Pal, Carmen ; Parkes, Kathy ; Pena, Mary Beth ; Rooney, Ellen S. ; van Wye, Gretchen E H ; Viscovich, Kristine A. ; Marrero, David ; Prince, Melvin J. ; Kelly, Susie M. ; Dotson, Yolanda F. ; Fineberg, Edwin S. ; Guare, John C. ; Hadden, Angela M. ; Ignaut, James M. ; Jackson, Marcia L. ; Kirkman, Marion S. ; Mather, Kieren ; Porter, Beverly D. ; Roach, Paris ; Rowland, Nancy D. ; Wheeler, Madelyn L. ; Ratner, Robert E. ; Youssef, Gretchen ; Shapiro, Sue ; Bavido-Arrage, Catherine ; Boggs, Geraldine ; Bronsord, Marjorie ; Brown, Ernestine ; Cheatham, Wayman W. ; Cola, Susan ; Evans, Cindy ; Gibbs, Peggy ; Kellum, Tracy ; Levatan, Claresa ; Nair, Asha K. ; Passaro, Maureen ; Uwaifo, Gabriel ; Saad, Mohammed F. ; Budget, Maria ; Jinagouda, Sujata ; Akbar, Khan ; Conzues, Claudia ; Magpuri, Perpetua ; Ngo, Kathy ; Rassam, Amer ; Waters, Debra ; Xapthalamous, Kathy ; Santiago, Julio V. ; Dagogo-Jack, Samuel ; White, Neil H. ; Das, Samia ; Santiago, Ana ; Brown, Angela ; Fisher, Edwin ; Hurt, Emma ; Jones, Tracy ; Kerr, Michelle ; Ryder, Lucy ; Wernimont, Cormarie ; Saudek, Christopher D. ; Bradley, Vanessa ; Sullivan, Emily ; Whittington, Tracy ; Abbas, Caroline ; Brancati, Frederick L. ; Clark, Jeanne M. ; Charleston, Jeanne B. ; Freel, Janice ; Horak, Katherine ; Jiggetts, Dawn ; Johnson, Deloris ; Joseph, Hope ; Loman, Kimberly ; Mosley, Henry ; Rubin, Richard R. ; Samuels, Alafia ; Stewart, Kerry J. ; Williamson, Paula ; Schade, David S. ; Adams, Karwyn S. ; Johannes, Carolyn ; Atler, Leslie F. ; Boyle, Patrick J. ; Burge, Mark R. ; Canady, Janene L. ; Chai, Lisa ; Gonzales, Ysela ; Hernandez-McGinnis, Doris A. ; Katz, Patricia ; King, Carolyn ; Rassam, Amer ; Rubinchik, Sofya ; Senter, Willette ; Waters, Debra ; Shamoon, Harry ; Brown, Janet O. ; Adorno, Elsie ; Cox, Liane ; Crandall, Jill ; Duffy, Helena ; Engel, Samuel ; Friedler, Allison ; Howard-Century, Crystal J. ; Kloiber, Stacey ; Longchamp, Nadege ; Martinez, Helen ; Pompi, Dorothy ; Scheindlin, Jonathan ; Violino, Elissa ; Walker, Elizabeth ; Wylie-Rosett, Judith ; Zimmerman, Elise ; Zonszein, Joel ; Orchard, Trevor ; Wing, Rena R. ; Koenning, Gaye ; Kramer, M. Kaye ; Barr, Susan ; Boraz, Miriam ; Clifford, Lisa ; Culyba, Rebecca ; Frazier, Marlene ; Gilligan, Ryan ; Harrier, Susan ; Harris, Louann ; Jeffries, Susan ; Kriska, Andrea ; Manjoo, Qurashia ; Mullen, Monica ; Noel, Alicia ; Otto, Amy ; Semler, Linda ; Smith, Cheryl F. ; Smith, Marie ; Venditti, Elizabeth ; Weinzierl, Valarie ; Williams, Katherine V. ; Wilson, Tara ; Arakaki, Richard F. ; Latimer, Renee W. ; Baker-Ladao, Narleen K. ; Beddow, Ralph ; Dias, Lorna ; Inouye, Jillian ; Mau, Marjorie K. ; Mikami, Kathy ; Mohideen, Pharis ; Odom, Sharon K. ; Perry, Raynette U. ; Knowler, William C. ; Cooeyate, Norman ; Hoskin, Mary A. ; Percy, Carol A. ; Acton, Kelly J. ; Andre, Vickie L. ; Barber, Rosalyn ; Begay, Shandiin ; Bennett, Peter H. ; Benson, Mary Beth ; Bird, Evelyn C. ; Broussard, Brenda A. ; Chavez, Marcella ; Dacawyma, Tara ; Doughty, Matthew S. ; Duncan, Roberta ; Edgerton, Cyndy ; Ghahate, Jacqueline M. ; Glass, Justin ; Glass, Martia ; Gohdes, Dorothy ; Grant, Wendy ; Hanson, Robert L. ; Horse, Ellie ; Ingraham, Louise E. ; Jackson, Merry ; Jay, Priscilla ; Kaskalla, Roylen S. ; Kessler, David ; Kobus, Kathleen M. ; Krakoff, Jonathan ; Manus, Catherine ; Michaels, Sara ; Morgan, Tina ; Nashboo, Yolanda ; Nelson, Julie A. ; Poirier, Steven ; Polczynski, Evette ; Reidy, Mike ; Roumain, Jeanine ; Rowse, Debra ; Sangster, Sandra ; Sewenemewa, Janet ; Tonemah, Darryl ; Wilson, Charlton ; Yazzie, Michelle ; Bain, Raymond ; Fowler, Sarah ; Brenneman, Tina ; Abebe, Solome ; Bamdad, Julie ; Callaghan, Jackie ; Edelstein, Sharon L. ; Gao, Yuping ; Grimes, Kristina L. ; Grover, Nisha ; Haffner, Lori ; Jones, Steve ; Jones, Tara L. ; Katz, Richard ; Lachin, John M. ; Mucik, Pamela ; Orlosky, Robert ; Rochon, James ; Sapozhnikova, Alla ; Sherif, Hanna ; Stimpson, Charlotte ; Temprosa, Marinella ; Walker-Murray, Fredricka ; Marcovina, Santica ; Strylewicz, Greg ; Aldrich, F. Alan ; O'Leary, Dan ; Stamm, Elizabeth ; Rautaharju, Pentti ; Prineas, Ronald J. ; Alexander, Teresa ; Campbell, Charles ; Hall, Sharon ; Li, Yabing ; Mills, Margaret ; Pemberton, Nancy ; Rautaharju, Farida ; Zhang, Zhuming ; Mayer-Davis, Elizabeth ; Moran, Robert R. ; Ganiats, Ted ; David, Kristin ; Sarkin, Andrew J. ; Eastman, R. ; Fradkin, Judith ; Garfield, Sanford ; Gregg, Edward ; Zhang, Ping ; Herman, William ; Florez, Jose C. ; Altshuler, David ; de Bakker, Paul I W ; Franks, Paul W. ; Hanson, Robert L. ; Jablonski, Kathleen ; Knowler, William C. ; McAteer, Jarred B. ; Pollin, Toni I. ; Shuldiner, Alan R. / Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment : The Diabetes Prevention Program. In: PLoS Genetics. 2012 ; Vol. 8, No. 8.
@article{1dfcc4f586c141aaabb39d53450723b2,
title = "Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program",
abstract = "Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.",
author = "Pollin, {Toni I.} and Tamara Isakova and Jablonski, {Kathleen A.} and {de Bakker}, {Paul I W} and Andrew Taylor and Jarred McAteer and Qing Pan and Horton, {Edward S.} and Delahanty, {Linda M.} and David Altshuler and Shuldiner, {Alan R.} and Goldberg, {Ronald B.} and Florez, {Jose C.} and Franks, {Paul W.} and Bray, {George A.} and Culbert, {Iris W.} and Champagne, {Catherine M.} and Barbara Eberhardt and Frank Greenway and Guillory, {Fonda G.} and Herbert, {April A.} and Jeffirs, {Michael L.} and Kennedy, {Betty M.} and Lovejoy, {Jennifer C.} and Morris, {Laura H.} and Melancon, {Lee E.} and Donna Ryan and Sanford, {Deborah A.} and Smith, {Kenneth G.} and Smith, {Lisa L.} and {St. Amant}, {Julia A.} and Tulley, {Richard T.} and Vicknair, {Paula C.} and Donald Williamson and Zachwieja, {Jeffery J.} and Polonsky, {Kenneth S.} and Janet Tobian and David Ehrmann and Matulik, {Margaret J.} and Bart Clark and Kirsten Czech and Catherine DeSandre and Ruthanne Hilbrich and Wylie McNabb and Semenske, {Ann R.} and Caro, {Jose F.} and Watson, {Pamela G.} and Goldstein, {Barry J.} and Smith, {Kellie A.} and Jewel Mendoza and Renee Liberoni and Constance Pepe and John Spandorfer and Donahue, {Richard P.} and Goldberg, {Ronald B.} and Ronald Prineas and Patricia Rowe and Jeanette Calles and Paul Cassanova-Romero and Florez, {Hermes J.} and Anna Giannella and Lascelles Kirby and Carmen Larreal and Valerie McLymont and Jadell Mendez and Juliet Ojito and Arlette Perry and Patrice Saab and Haffner, {Steven M.} and Montez, {Maria G.} and Carlos Lorenzo and Arlene Martinez and Hamman, {Richard F.} and Nash, {Patricia V.} and Lisa Testaverde and Anderson, {Denise R.} and Ballonoff, {Larry B.} and Alexis Bouffard and Calonge, {B. Ned} and Lynne Delve and Martha Farago and Hill, {James O.} and Hoyer, {Shelley R.} and Jortberg, {Bonnie T.} and Dione Lenz and Marsha Miller and Price, {David W.} and Regensteiner, {Judith G.} and Helen Seagle and Smith, {Carissa M.} and Steinke, {Sheila C.} and Brent VanDorsten and Horton, {Edward S.} and Lawton, {Kathleen E.} and Arky, {Ronald A.} and Marybeth Bryant and Burke, {Jacqueline P.} and Enrique Caballero and Callaphan, {Karen M.} and Ganda, {Om P.} and Therese Franklin and Jackson, {Sharon D.} and Jacobsen, {Alan M.} and Jacobsen, {Alan M.} and Kula, {Lyn M.} and Margaret Kocal and Malloy, {Maureen A.} and Maryanne Nicosia and Oldmixon, {Cathryn F.} and Jocelyn Pan and Marizel Quitingon and Stacy Rubtchinsky and Seely, {Ellen W.} and Dana Schweizer and Donald Simonson and Fannie Smith and Solomon, {Caren G.} and James Warram and Kahn, {Steven E.} and Montgomery, {Brenda K.} and Wilfred Fujimoto and Knopp, {Robert H.} and Lipkin, {Edward W.} and Michelle Marr and Dace Trence and Kitabchi, {Abbas E.} and Murphy, {Mary E.} and Applegate, {William B.} and Michael Bryer-Ash and Frieson, {Sandra L.} and Raed Imseis and Helen Lambeth and Lichtermann, {Lynne C.} and Hooman Oktaei and Rutledge, {Lily M K} and Sherman, {Amy R.} and Smith, {Clara M.} and Soberman, {Judith E.} and Beverly Williams-Cleaves and Metzger, {Boyd E.} and Johnson, {Mariana K.} and Catherine Behrends and Michelle Cook and Marian Fitzgibbon and Giles, {Mimi M.} and Deloris Heard and Johnson, {Cheryl K H} and Diane Larsen and Anne Lowe and Megan Lyman and David McPherson and Molitch, {Mark E.} and Thomas Pitts and Renee Reinhart and Susan Roston and Schinleber, {Pamela A.} and Nathan, {David M.} and Charles McKitrick and Heather Turgeon and Kathy Abbott and Ellen Anderson and Laurie Bissett and Enrico Cagliero and Florez, {Jose C.} and Linda Delahanty and Valerie Goldman and Alexandra Poulos and Olefsky, {Jerrold M.} and Carrion-Petersen, {Mary Lou} and Elizabeth Barrett-Connor and Edelman, {Steven V.} and Henry, {Robert R.} and Javiva Horne and Janesch, {Simona Szerdi} and Diana Leos and Sundar Mudaliar and William Polonsky and Jean Smith and Karen Vejvoda and Pi-Sunyer, {F. Xavier} and Lee, {Jane E.} and Allison, {David B.} and Aronoff, {Nancy J.} and Crandall, {Jill P.} and Foo, {Sandra T.} and Carmen Pal and Kathy Parkes and Pena, {Mary Beth} and Rooney, {Ellen S.} and {van Wye}, {Gretchen E H} and Viscovich, {Kristine A.} and David Marrero and Prince, {Melvin J.} and Kelly, {Susie M.} and Dotson, {Yolanda F.} and Fineberg, {Edwin S.} and Guare, {John C.} and Hadden, {Angela M.} and Ignaut, {James M.} and Jackson, {Marcia L.} and Kirkman, {Marion S.} and Kieren Mather and Porter, {Beverly D.} and Paris Roach and Rowland, {Nancy D.} and Wheeler, {Madelyn L.} and Ratner, {Robert E.} and Gretchen Youssef and Sue Shapiro and Catherine Bavido-Arrage and Geraldine Boggs and Marjorie Bronsord and Ernestine Brown and Cheatham, {Wayman W.} and Susan Cola and Cindy Evans and Peggy Gibbs and Tracy Kellum and Claresa Levatan and Nair, {Asha K.} and Maureen Passaro and Gabriel Uwaifo and Saad, {Mohammed F.} and Maria Budget and Sujata Jinagouda and Khan Akbar and Claudia Conzues and Perpetua Magpuri and Kathy Ngo and Amer Rassam and Debra Waters and Kathy Xapthalamous and Santiago, {Julio V.} and Samuel Dagogo-Jack and White, {Neil H.} and Samia Das and Ana Santiago and Angela Brown and Edwin Fisher and Emma Hurt and Tracy Jones and Michelle Kerr and Lucy Ryder and Cormarie Wernimont and Saudek, {Christopher D.} and Vanessa Bradley and Emily Sullivan and Tracy Whittington and Caroline Abbas and Brancati, {Frederick L.} and Clark, {Jeanne M.} and Charleston, {Jeanne B.} and Janice Freel and Katherine Horak and Dawn Jiggetts and Deloris Johnson and Hope Joseph and Kimberly Loman and Henry Mosley and Rubin, {Richard R.} and Alafia Samuels and Stewart, {Kerry J.} and Paula Williamson and Schade, {David S.} and Adams, {Karwyn S.} and Carolyn Johannes and Atler, {Leslie F.} and Boyle, {Patrick J.} and Burge, {Mark R.} and Canady, {Janene L.} and Lisa Chai and Ysela Gonzales and Hernandez-McGinnis, {Doris A.} and Patricia Katz and Carolyn King and Amer Rassam and Sofya Rubinchik and Willette Senter and Debra Waters and Harry Shamoon and Brown, {Janet O.} and Elsie Adorno and Liane Cox and Jill Crandall and Helena Duffy and Samuel Engel and Allison Friedler and Howard-Century, {Crystal J.} and Stacey Kloiber and Nadege Longchamp and Helen Martinez and Dorothy Pompi and Jonathan Scheindlin and Elissa Violino and Elizabeth Walker and Judith Wylie-Rosett and Elise Zimmerman and Joel Zonszein and Trevor Orchard and Wing, {Rena R.} and Gaye Koenning and Kramer, {M. Kaye} and Susan Barr and Miriam Boraz and Lisa Clifford and Rebecca Culyba and Marlene Frazier and Ryan Gilligan and Susan Harrier and Louann Harris and Susan Jeffries and Andrea Kriska and Qurashia Manjoo and Monica Mullen and Alicia Noel and Amy Otto and Linda Semler and Smith, {Cheryl F.} and Marie Smith and Elizabeth Venditti and Valarie Weinzierl and Williams, {Katherine V.} and Tara Wilson and Arakaki, {Richard F.} and Latimer, {Renee W.} and Baker-Ladao, {Narleen K.} and Ralph Beddow and Lorna Dias and Jillian Inouye and Mau, {Marjorie K.} and Kathy Mikami and Pharis Mohideen and Odom, {Sharon K.} and Perry, {Raynette U.} and Knowler, {William C.} and Norman Cooeyate and Hoskin, {Mary A.} and Percy, {Carol A.} and Acton, {Kelly J.} and Andre, {Vickie L.} and Rosalyn Barber and Shandiin Begay and Bennett, {Peter H.} and Benson, {Mary Beth} and Bird, {Evelyn C.} and Broussard, {Brenda A.} and Marcella Chavez and Tara Dacawyma and Doughty, {Matthew S.} and Roberta Duncan and Cyndy Edgerton and Ghahate, {Jacqueline M.} and Justin Glass and Martia Glass and Dorothy Gohdes and Wendy Grant and Hanson, {Robert L.} and Ellie Horse and Ingraham, {Louise E.} and Merry Jackson and Priscilla Jay and Kaskalla, {Roylen S.} and David Kessler and Kobus, {Kathleen M.} and Jonathan Krakoff and Catherine Manus and Sara Michaels and Tina Morgan and Yolanda Nashboo and Nelson, {Julie A.} and Steven Poirier and Evette Polczynski and Mike Reidy and Jeanine Roumain and Debra Rowse and Sandra Sangster and Janet Sewenemewa and Darryl Tonemah and Charlton Wilson and Michelle Yazzie and Raymond Bain and Sarah Fowler and Tina Brenneman and Solome Abebe and Julie Bamdad and Jackie Callaghan and Edelstein, {Sharon L.} and Yuping Gao and Grimes, {Kristina L.} and Nisha Grover and Lori Haffner and Steve Jones and Jones, {Tara L.} and Richard Katz and Lachin, {John M.} and Pamela Mucik and Robert Orlosky and James Rochon and Alla Sapozhnikova and Hanna Sherif and Charlotte Stimpson and Marinella Temprosa and Fredricka Walker-Murray and Santica Marcovina and Greg Strylewicz and Aldrich, {F. Alan} and Dan O'Leary and Elizabeth Stamm and Pentti Rautaharju and Prineas, {Ronald J.} and Teresa Alexander and Charles Campbell and Sharon Hall and Yabing Li and Margaret Mills and Nancy Pemberton and Farida Rautaharju and Zhuming Zhang and Elizabeth Mayer-Davis and Moran, {Robert R.} and Ted Ganiats and Kristin David and Sarkin, {Andrew J.} and R. Eastman and Judith Fradkin and Sanford Garfield and Edward Gregg and Ping Zhang and William Herman and Florez, {Jose C.} and David Altshuler and {de Bakker}, {Paul I W} and Franks, {Paul W.} and Hanson, {Robert L.} and Kathleen Jablonski and Knowler, {William C.} and McAteer, {Jarred B.} and Pollin, {Toni I.} and Shuldiner, {Alan R.}",
year = "2012",
month = "8",
doi = "10.1371/journal.pgen.1002895",
language = "English",
volume = "8",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment

T2 - The Diabetes Prevention Program

AU - Pollin, Toni I.

AU - Isakova, Tamara

AU - Jablonski, Kathleen A.

AU - de Bakker, Paul I W

AU - Taylor, Andrew

AU - McAteer, Jarred

AU - Pan, Qing

AU - Horton, Edward S.

AU - Delahanty, Linda M.

AU - Altshuler, David

AU - Shuldiner, Alan R.

AU - Goldberg, Ronald B.

AU - Florez, Jose C.

AU - Franks, Paul W.

AU - Bray, George A.

AU - Culbert, Iris W.

AU - Champagne, Catherine M.

AU - Eberhardt, Barbara

AU - Greenway, Frank

AU - Guillory, Fonda G.

AU - Herbert, April A.

AU - Jeffirs, Michael L.

AU - Kennedy, Betty M.

AU - Lovejoy, Jennifer C.

AU - Morris, Laura H.

AU - Melancon, Lee E.

AU - Ryan, Donna

AU - Sanford, Deborah A.

AU - Smith, Kenneth G.

AU - Smith, Lisa L.

AU - St. Amant, Julia A.

AU - Tulley, Richard T.

AU - Vicknair, Paula C.

AU - Williamson, Donald

AU - Zachwieja, Jeffery J.

AU - Polonsky, Kenneth S.

AU - Tobian, Janet

AU - Ehrmann, David

AU - Matulik, Margaret J.

AU - Clark, Bart

AU - Czech, Kirsten

AU - DeSandre, Catherine

AU - Hilbrich, Ruthanne

AU - McNabb, Wylie

AU - Semenske, Ann R.

AU - Caro, Jose F.

AU - Watson, Pamela G.

AU - Goldstein, Barry J.

AU - Smith, Kellie A.

AU - Mendoza, Jewel

AU - Liberoni, Renee

AU - Pepe, Constance

AU - Spandorfer, John

AU - Donahue, Richard P.

AU - Goldberg, Ronald B.

AU - Prineas, Ronald

AU - Rowe, Patricia

AU - Calles, Jeanette

AU - Cassanova-Romero, Paul

AU - Florez, Hermes J.

AU - Giannella, Anna

AU - Kirby, Lascelles

AU - Larreal, Carmen

AU - McLymont, Valerie

AU - Mendez, Jadell

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AU - Marcovina, Santica

AU - Strylewicz, Greg

AU - Aldrich, F. Alan

AU - O'Leary, Dan

AU - Stamm, Elizabeth

AU - Rautaharju, Pentti

AU - Prineas, Ronald J.

AU - Alexander, Teresa

AU - Campbell, Charles

AU - Hall, Sharon

AU - Li, Yabing

AU - Mills, Margaret

AU - Pemberton, Nancy

AU - Rautaharju, Farida

AU - Zhang, Zhuming

AU - Mayer-Davis, Elizabeth

AU - Moran, Robert R.

AU - Ganiats, Ted

AU - David, Kristin

AU - Sarkin, Andrew J.

AU - Eastman, R.

AU - Fradkin, Judith

AU - Garfield, Sanford

AU - Gregg, Edward

AU - Zhang, Ping

AU - Herman, William

AU - Florez, Jose C.

AU - Altshuler, David

AU - de Bakker, Paul I W

AU - Franks, Paul W.

AU - Hanson, Robert L.

AU - Jablonski, Kathleen

AU - Knowler, William C.

AU - McAteer, Jarred B.

AU - Pollin, Toni I.

AU - Shuldiner, Alan R.

PY - 2012/8

Y1 - 2012/8

N2 - Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

AB - Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1×10-17). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial {pipe}r{pipe} = 0.07-0.17, P = 5×10-5-1×10-19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10-5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = -0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

UR - http://www.scopus.com/inward/record.url?scp=84866155075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866155075&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1002895

DO - 10.1371/journal.pgen.1002895

M3 - Article

C2 - 22951888

AN - SCOPUS:84866155075

VL - 8

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 8

M1 - e1002895

ER -