Adams, L.A.

Ang, W.Q.

Ayonrinde, O.T.

Beilin, L.J.

Lye, S.J.

Mori, T.A.

Oddy, W.H.

Olynyk, J.K.

Palmer, L.J.

Pennell, C.E.

English

Research Repository

257LIPID METABOLISM GENE POLYMORPHISMS AND RISKOF FATTY LIVER IN ADOLESCENTS: A POPULATIONBASED COHORT STUDYLeon A. Adams1, Wei Q. Ang2, Oyekoya T. Ayonrinde1, John K.Olynyk1, Lawrie J. Beilin1, Trevor A. Mori1, Lyle J. Palmer3, WendyH. Oddy4, Stephen J. Lye5, Craig E. Pennell2; 1Medicine and Phar-macology, University of Western Australia, Nedlands, WA, Aus-tralia; 2Womens and Infant Health, University of Western Australia,Nedlands, WA, Australia; 3Centre for Genetic Epidemiology andBiostatistics, University of Western Australia, Nedlands, WA, Aus-tralia; 4Telethon Institute of Child Health Research, University ofWestern Australia, Subiaco, WA, Australia; 5Samuel LunefeldResearch Institute, Mt Siani, Toronto, ON, CanadaNonalcoholic fatty liver disease (NAFLD) is a heritable diseaseresulting from altered hepatic triglyceride metabolism. Weexamined the association between polymorphisms in genesinvolved in hepatic triglyceride hydrolysis and transport andfatty liver in a population based cohort of adolescents. Meth-ods: Adolescents (n=1,170) from the population-based WesternAustralian Pregnancy (Raine) Birth Cohort underwent detailedphenotypic characterisation at age 17 including hepatic ultra-sound, detailed questionnaires, anthropometry and biochemi-cal testing. DNA was extracted and 32 SNPs in lipidmetabolism genes (ApoB100, ATGL, ABHD5, MTTP, CETP) witha minor allele frequency >0.1 were genotyped. Multivariatemodelling was used to investigate associations between SNPsand fatty liver. Final analyses focused on 773 Caucasian ado-lescents with complete phenotype and genotype data. Multipletesting was accounted for using a false discovery rate of 10%.Results: Fatty liver was diagnosed by ultrasound in 133/773(17.2%) of the Raine participants (12.7% male vs. 21.8%female, p=0.001). Adolescents with fatty liver had higher meas-ures of adiposity (skin fold-thickness, BMI, waist circumference)and insulin resistance (HOMA-IR) than adolescents without fattyliver (all P<0.001). No significant associations were identifiedbetween ALT or serum triglyceride and the 32 SNPS. In bothsexes, the minor allele of rs3774792 (abhydrolase domaincontaining 5 (ABHD5) gene) was associated with an increasedrisk of fatty liver (OR=2.54, 95%CI 1.41-4.58, p=0.002). Infemales, but not males, the minor alleles in two SNPS in cho-lesterol ester transport protein (CETP) gene were associatedwith reduced risk of fatty liver: rs12447924 (OR 0.21, 95% CI0.07-0.59, p=0.003) and rs12597002 (OR=0.24, 95%CI0.10-0.56, p=0.001). These two SNPs are in linkage disequi-librium (r2=0.6, D’=0.94). These associations were independ-ent of BMI, skin fold thickness, HOMA-IR, HDL, triglyceride,ALT, alcohol intake, gestational age, birth weight and measuresof nutrition. There was no interaction between SNP’s and meas-ures of adiposity. The associations between SNPs in ABHD5,CETP and fatty liver were independent with the presence offour adverse alleles increasing the risk of fatty liver nearly 8-fold(OR 7.77, 95%CI 2.67-22.63, p<0.001). Conclusions: Poly-morphisms in lipid metabolism genes are associated with fattyHEPATOLOGY, VOLUME 52, NUMBER 4 (SUPPL) AASLD ABSTRACTS 451Aliver in adolescence, independent of metabolic factors, nutri-tion, alcohol and measures of growth. Whilst these resultsrequire replication in other populations, they may offer possi-bilities for early prediction of fatty liver and targeted interven-tions.Disclosures:John K. Olynyk - Grant/Research Support: Roche, BayerThe following people have nothing to disclose: Leon A. Adams, Wei Q. Ang,Oyekoya T. Ayonrinde, Lawrie J. Beilin, Trevor A. Mori, Lyle J. Palmer, Wendy H.Oddy, Stephen J. Lye, Craig E. Pennell452A AASLD ABSTRACTS HEPATOLOGY, October, 2010

Lipid metabolism gene polymorphisms and risk of fatty liver in adolecents: A population based cohort study

https://researchrepository.murdoch.edu.au/id/eprint/20365/1/lipid_metabolism.pdf

Lipid metabolism gene polymorphisms and risk of fatty liver in adolecents: A population based cohort study

Abstract

Similar works

Full text

Available Versions

Research Repository