A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults: A population-based study

Peiqin Li, Jing Zhao, Kumar S.D. Kothapalli, Xiang Li, Hui Li, Yuxuan Han, Shengquan Mi, Wenhua Zhao, Qizhai Li, Hong Zhang, Yiqing Song, J. Thomas Brenna, Ying Gao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. Objective This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Design Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. Results A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n-6 AA and the ratio of AA to n-3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = -0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. Conclusions The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia.

Original languageEnglish (US)
Pages (from-to)867-875
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume107
Issue number6
DOIs
StatePublished - Jun 1 2018

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Multigene Family
Unsaturated Fatty Acids
Arachidonic Acid
Eicosapentaenoic Acid
Lipids
Fatty Acid Desaturases
Genotype
Population
Docosahexaenoic Acids
Base Pairing
Alleles
Phenotype
Eicosanoids
Agar Gel Electrophoresis
Sterols
Dyslipidemias
Gas Chromatography
Introns
HDL Cholesterol
Linear Models

Keywords

  • dyslipidemia
  • fatty acid desaturases
  • gene polymorphism
  • insertion-deletion
  • long-chain polyunsaturated fatty acids

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults : A population-based study. / Li, Peiqin; Zhao, Jing; Kothapalli, Kumar S.D.; Li, Xiang; Li, Hui; Han, Yuxuan; Mi, Shengquan; Zhao, Wenhua; Li, Qizhai; Zhang, Hong; Song, Yiqing; Brenna, J. Thomas; Gao, Ying.

In: American Journal of Clinical Nutrition, Vol. 107, No. 6, 01.06.2018, p. 867-875.

Research output: Contribution to journalArticle

Li, Peiqin ; Zhao, Jing ; Kothapalli, Kumar S.D. ; Li, Xiang ; Li, Hui ; Han, Yuxuan ; Mi, Shengquan ; Zhao, Wenhua ; Li, Qizhai ; Zhang, Hong ; Song, Yiqing ; Brenna, J. Thomas ; Gao, Ying. / A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults : A population-based study. In: American Journal of Clinical Nutrition. 2018 ; Vol. 107, No. 6. pp. 867-875.
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title = "A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults: A population-based study",
abstract = "Background Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. Objective This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Design Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. Results A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n-6 AA and the ratio of AA to n-3 EPA plus docosahexaenoic acid (DHA) were 57{\%} and 32{\%} higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = -0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. Conclusions The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia.",
keywords = "dyslipidemia, fatty acid desaturases, gene polymorphism, insertion-deletion, long-chain polyunsaturated fatty acids",
author = "Peiqin Li and Jing Zhao and Kothapalli, {Kumar S.D.} and Xiang Li and Hui Li and Yuxuan Han and Shengquan Mi and Wenhua Zhao and Qizhai Li and Hong Zhang and Yiqing Song and Brenna, {J. Thomas} and Ying Gao",
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TY - JOUR

T1 - A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults

T2 - A population-based study

AU - Li, Peiqin

AU - Zhao, Jing

AU - Kothapalli, Kumar S.D.

AU - Li, Xiang

AU - Li, Hui

AU - Han, Yuxuan

AU - Mi, Shengquan

AU - Zhao, Wenhua

AU - Li, Qizhai

AU - Zhang, Hong

AU - Song, Yiqing

AU - Brenna, J. Thomas

AU - Gao, Ying

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. Objective This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Design Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. Results A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n-6 AA and the ratio of AA to n-3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = -0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. Conclusions The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia.

AB - Background Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. Objective This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Design Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. Results A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n-6 AA and the ratio of AA to n-3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = -0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. Conclusions The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia.

KW - dyslipidemia

KW - fatty acid desaturases

KW - gene polymorphism

KW - insertion-deletion

KW - long-chain polyunsaturated fatty acids

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