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Table of Contents
Vol. 75, No. 1, 2013
Issue release date: May 2013
Section title: Original Paper
Free Access
Hum Hered 2013;75:34-43

Genetic Variation at NCAN Locus Is Associated with Inflammation and Fibrosis in Non-Alcoholic Fatty Liver Disease in Morbid Obesity

Gorden A.a, c · Yang R.b, c · Yerges-Armstrong L.M.b, c · Ryan K.A.b, c · Speliotes E.d · Borecki I.B.e · Harris T.B.f · Chu X.g · Wood G.C.g · Still C.D.g · Shuldiner A.R.b,c,h · Gerhard G.S.g · the GOLD Consortium1
Divisions of aGastroenterology and bEndocrinology, Diabetes and Nutrition, and cProgram in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Md., dUniversity of Michigan School of Medicine, Ann Arbor, Mich., eDivision of Statistical Genomics, Washington University School of Medicine, St. Louis, Mo., fLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Md., gGeisinger Clinic Obesity Institute, Danville, Pa., and hGeriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Md., USA
email Corresponding Author

Glenn S. Gerhard, MD

Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine

Pennsylvania State University College of Medicine

Hershey, PA 17033 (USA)

E-mail ggerhard@hmc.psu.edu

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Objective: Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near PNPLA3, NCAN, GCKR, LYPLAL1 and PPP1R3B were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity. Methods: In 1,092 bariatric surgery patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed. Results: We replicated the association of hepatosteatosis with PNPLA3 rs738409[G] and with NCAN rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. rs2228603[T] was associated with lower serum low-density lipoprotein, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD. Conclusion:NCAN rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis.

© 2013 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 21, 2012
Accepted: November 27, 2012
Published online: April 10, 2013
Issue release date: May 2013

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 3

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

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