Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease

Samer Gawrieh, Tesfaye M. Baye, Melanie Carless, James Wallace, Richard Komorowski, David E. Kleiner, Deborah Andris, Bassem Makladi, Regina Cole, Michael Charlton, Joanne Curran, Thomas D. Dyer, Jac Charlesworth, Russell Wilke, John Blangero, Ahmed H. Kissebah, Michael Olivier

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Genetic factors alter the risk for nonalcoholic fatty liver disease (NAFLD). We sought to identify NAFLD-associated genes and elucidate gene networks and pathways involved in the pathogenesis of NAFLD. Methods: Quantitative global hepatic gene expression analysis was performed on 53 morbidly obese Caucasian subjects undergoing bariatric surgery (27 with NAFLD and 26 controls). After standardization of data, gene expression profiles were compared between patients with NAFLD and controls. The set of genes that significantly correlated with NAFLD was further analyzed by hierarchical clustering and ingenuity pathways analyses. Results: There were 25,643 quantitative transcripts, of which 108 were significantly associated with NAFLD (p∈<∈0.001). Canonical pathway analysis in the NAFLD-associated gene clusters showed that the hepatic fibrosis signaling was the most significant pathway in the up-regulated NAFLD gene cluster containing three (COL1A1, IL10, IGFBP3) significantly altered genes, whereas the endoplasmic reticulum stress and protein ubiquitination pathways were the most significant pathways in the down-regulated NAFLD gene cluster, with the first pathway containing one (HSPA5) and the second containing two (HSPA5, USP25) significantly altered genes. The four primary gene networks associated with NAFLD were involved in cell death, immunological disease, cellular movement, and lipid metabolism with several significantly altered "hub" genes in these networks. Conclusions: This study reveals the canonical pathways and gene networks associated with NAFLD in morbidly obese Caucasians. The application of gene network analysis highlights the transcriptional relationships among NAFLD-associated genes and allows identification of hub genes that may represent high-priority candidates for NAFLD.

Original languageEnglish (US)
Pages (from-to)1698-1709
Number of pages12
JournalObesity Surgery
Volume20
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Fingerprint

Gene Regulatory Networks
Liver
Multigene Family
Genes
Non-alcoholic Fatty Liver Disease
Endoplasmic Reticulum Stress
Bariatric Surgery
Ubiquitination
Immune System Diseases
Heat-Shock Proteins
Lipid Metabolism
Transcriptome
Interleukin-10
Cluster Analysis

Keywords

  • Fatty liver
  • Gene expression
  • Gene networks
  • Genes
  • NAFLD
  • Pathogenesis

ASJC Scopus subject areas

  • Surgery
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Gawrieh, S., Baye, T. M., Carless, M., Wallace, J., Komorowski, R., Kleiner, D. E., ... Olivier, M. (2010). Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease. Obesity Surgery, 20(12), 1698-1709. https://doi.org/10.1007/s11695-010-0171-6

Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease. / Gawrieh, Samer; Baye, Tesfaye M.; Carless, Melanie; Wallace, James; Komorowski, Richard; Kleiner, David E.; Andris, Deborah; Makladi, Bassem; Cole, Regina; Charlton, Michael; Curran, Joanne; Dyer, Thomas D.; Charlesworth, Jac; Wilke, Russell; Blangero, John; Kissebah, Ahmed H.; Olivier, Michael.

In: Obesity Surgery, Vol. 20, No. 12, 12.2010, p. 1698-1709.

Research output: Contribution to journalArticle

Gawrieh, S, Baye, TM, Carless, M, Wallace, J, Komorowski, R, Kleiner, DE, Andris, D, Makladi, B, Cole, R, Charlton, M, Curran, J, Dyer, TD, Charlesworth, J, Wilke, R, Blangero, J, Kissebah, AH & Olivier, M 2010, 'Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease', Obesity Surgery, vol. 20, no. 12, pp. 1698-1709. https://doi.org/10.1007/s11695-010-0171-6
Gawrieh, Samer ; Baye, Tesfaye M. ; Carless, Melanie ; Wallace, James ; Komorowski, Richard ; Kleiner, David E. ; Andris, Deborah ; Makladi, Bassem ; Cole, Regina ; Charlton, Michael ; Curran, Joanne ; Dyer, Thomas D. ; Charlesworth, Jac ; Wilke, Russell ; Blangero, John ; Kissebah, Ahmed H. ; Olivier, Michael. / Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease. In: Obesity Surgery. 2010 ; Vol. 20, No. 12. pp. 1698-1709.
@article{d73681854ae64e81b13c66edf7e2359c,
title = "Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease",
abstract = "Background: Genetic factors alter the risk for nonalcoholic fatty liver disease (NAFLD). We sought to identify NAFLD-associated genes and elucidate gene networks and pathways involved in the pathogenesis of NAFLD. Methods: Quantitative global hepatic gene expression analysis was performed on 53 morbidly obese Caucasian subjects undergoing bariatric surgery (27 with NAFLD and 26 controls). After standardization of data, gene expression profiles were compared between patients with NAFLD and controls. The set of genes that significantly correlated with NAFLD was further analyzed by hierarchical clustering and ingenuity pathways analyses. Results: There were 25,643 quantitative transcripts, of which 108 were significantly associated with NAFLD (p∈<∈0.001). Canonical pathway analysis in the NAFLD-associated gene clusters showed that the hepatic fibrosis signaling was the most significant pathway in the up-regulated NAFLD gene cluster containing three (COL1A1, IL10, IGFBP3) significantly altered genes, whereas the endoplasmic reticulum stress and protein ubiquitination pathways were the most significant pathways in the down-regulated NAFLD gene cluster, with the first pathway containing one (HSPA5) and the second containing two (HSPA5, USP25) significantly altered genes. The four primary gene networks associated with NAFLD were involved in cell death, immunological disease, cellular movement, and lipid metabolism with several significantly altered {"}hub{"} genes in these networks. Conclusions: This study reveals the canonical pathways and gene networks associated with NAFLD in morbidly obese Caucasians. The application of gene network analysis highlights the transcriptional relationships among NAFLD-associated genes and allows identification of hub genes that may represent high-priority candidates for NAFLD.",
keywords = "Fatty liver, Gene expression, Gene networks, Genes, NAFLD, Pathogenesis",
author = "Samer Gawrieh and Baye, {Tesfaye M.} and Melanie Carless and James Wallace and Richard Komorowski and Kleiner, {David E.} and Deborah Andris and Bassem Makladi and Regina Cole and Michael Charlton and Joanne Curran and Dyer, {Thomas D.} and Jac Charlesworth and Russell Wilke and John Blangero and Kissebah, {Ahmed H.} and Michael Olivier",
year = "2010",
month = "12",
doi = "10.1007/s11695-010-0171-6",
language = "English (US)",
volume = "20",
pages = "1698--1709",
journal = "Obesity Surgery",
issn = "0960-8923",
publisher = "Springer New York",
number = "12",

}

TY - JOUR

T1 - Hepatic gene networks in morbidly obese patients with nonalcoholic fatty liver disease

AU - Gawrieh, Samer

AU - Baye, Tesfaye M.

AU - Carless, Melanie

AU - Wallace, James

AU - Komorowski, Richard

AU - Kleiner, David E.

AU - Andris, Deborah

AU - Makladi, Bassem

AU - Cole, Regina

AU - Charlton, Michael

AU - Curran, Joanne

AU - Dyer, Thomas D.

AU - Charlesworth, Jac

AU - Wilke, Russell

AU - Blangero, John

AU - Kissebah, Ahmed H.

AU - Olivier, Michael

PY - 2010/12

Y1 - 2010/12

N2 - Background: Genetic factors alter the risk for nonalcoholic fatty liver disease (NAFLD). We sought to identify NAFLD-associated genes and elucidate gene networks and pathways involved in the pathogenesis of NAFLD. Methods: Quantitative global hepatic gene expression analysis was performed on 53 morbidly obese Caucasian subjects undergoing bariatric surgery (27 with NAFLD and 26 controls). After standardization of data, gene expression profiles were compared between patients with NAFLD and controls. The set of genes that significantly correlated with NAFLD was further analyzed by hierarchical clustering and ingenuity pathways analyses. Results: There were 25,643 quantitative transcripts, of which 108 were significantly associated with NAFLD (p∈<∈0.001). Canonical pathway analysis in the NAFLD-associated gene clusters showed that the hepatic fibrosis signaling was the most significant pathway in the up-regulated NAFLD gene cluster containing three (COL1A1, IL10, IGFBP3) significantly altered genes, whereas the endoplasmic reticulum stress and protein ubiquitination pathways were the most significant pathways in the down-regulated NAFLD gene cluster, with the first pathway containing one (HSPA5) and the second containing two (HSPA5, USP25) significantly altered genes. The four primary gene networks associated with NAFLD were involved in cell death, immunological disease, cellular movement, and lipid metabolism with several significantly altered "hub" genes in these networks. Conclusions: This study reveals the canonical pathways and gene networks associated with NAFLD in morbidly obese Caucasians. The application of gene network analysis highlights the transcriptional relationships among NAFLD-associated genes and allows identification of hub genes that may represent high-priority candidates for NAFLD.

AB - Background: Genetic factors alter the risk for nonalcoholic fatty liver disease (NAFLD). We sought to identify NAFLD-associated genes and elucidate gene networks and pathways involved in the pathogenesis of NAFLD. Methods: Quantitative global hepatic gene expression analysis was performed on 53 morbidly obese Caucasian subjects undergoing bariatric surgery (27 with NAFLD and 26 controls). After standardization of data, gene expression profiles were compared between patients with NAFLD and controls. The set of genes that significantly correlated with NAFLD was further analyzed by hierarchical clustering and ingenuity pathways analyses. Results: There were 25,643 quantitative transcripts, of which 108 were significantly associated with NAFLD (p∈<∈0.001). Canonical pathway analysis in the NAFLD-associated gene clusters showed that the hepatic fibrosis signaling was the most significant pathway in the up-regulated NAFLD gene cluster containing three (COL1A1, IL10, IGFBP3) significantly altered genes, whereas the endoplasmic reticulum stress and protein ubiquitination pathways were the most significant pathways in the down-regulated NAFLD gene cluster, with the first pathway containing one (HSPA5) and the second containing two (HSPA5, USP25) significantly altered genes. The four primary gene networks associated with NAFLD were involved in cell death, immunological disease, cellular movement, and lipid metabolism with several significantly altered "hub" genes in these networks. Conclusions: This study reveals the canonical pathways and gene networks associated with NAFLD in morbidly obese Caucasians. The application of gene network analysis highlights the transcriptional relationships among NAFLD-associated genes and allows identification of hub genes that may represent high-priority candidates for NAFLD.

KW - Fatty liver

KW - Gene expression

KW - Gene networks

KW - Genes

KW - NAFLD

KW - Pathogenesis

UR - http://www.scopus.com/inward/record.url?scp=78650690095&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650690095&partnerID=8YFLogxK

U2 - 10.1007/s11695-010-0171-6

DO - 10.1007/s11695-010-0171-6

M3 - Article

C2 - 20473581

AN - SCOPUS:78650690095

VL - 20

SP - 1698

EP - 1709

JO - Obesity Surgery

JF - Obesity Surgery

SN - 0960-8923

IS - 12

ER -