Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity

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dc.contributor.authorAdams, L.
dc.contributor.authorMarsh, J.
dc.contributor.authorAyonrinde, O.
dc.contributor.authorOlynyk, J.
dc.contributor.authorAng, W.
dc.contributor.authorBeilin, L.
dc.contributor.authorMori, T.
dc.contributor.authorPalmer, L.
dc.contributor.authorOddy, W.
dc.contributor.authorLye, S.
dc.contributor.authorPennell, C.
dc.date.issued2012
dc.description.abstract<h4>Background and aim</h4>Environmental factors including excessive caloric intake lead to disordered lipid metabolism and fatty liver disease (FLD). However, FLD demonstrates heritability suggesting genetic factors are also important. We aimed to use a candidate gene approach to examine the association between FLD and single nucleotide polymorphisms (SNPs) in lipid metabolism genes in the adolescent population-based Western Australian Pregnancy (Raine) Cohort.<h4>Methods</h4>A total 951 seventeen year-olds underwent hepatic ultrasound, anthropometric and biochemical characterization, DNA extraction and genotyping for 57 SNPs in seven lipid metabolism genes (ApoB100, ATGL, ABHD5, MTTP, CETP, SREBP-1c, PPARα). Associations were adjusted for metabolic factors and Bonferroni corrected.<h4>Results</h4>The prevalence of FLD was 16.2% (11.4% male vs 21.2% female, P=0.001). Multivariate analysis of metabolic factors found suprailiac skinfold thickness (SST) to be the major predictor of FLD in females and males (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.08-1.15, P=1.7×10(-10) and OR 1.17, 95%CI 1.13-1.22, P=2.4×10(-11) , respectively). In females, two SNPs in linkage disequilibrium from the CETP gene were associated with FLD: rs12447924 (OR 2.16, 95%CI 1.42-3.32, P=0.0003) and rs12597002 (OR=2.22, 95%CI 1.46-3.41 P=0.0002). In lean homozygotes, the probability of FLD was over 30%, compared with 10-15% in lean heterozygotes and 3-5% in lean wild-types. However, these associations were modified by SST, such that for obese individuals, the probability of FLD was over 30% in all genotype groups.<h4>Conclusions</h4>Cholesteryl ester transfer protein gene polymorphisms are associated with an increased risk of FLD in adolescent females. The effect is independent of adiposity in homozygotes, thereby placing lean individuals at a significant risk of FLD.
dc.description.statementofresponsibilityLeon A Adams, Julie A Marsh, Oyekoya T Ayonrinde, John K Olynyk, Wei Q Ang, Lawrence J Beilin, Trevor Mori, Lyle J Palmer, Wendy W Oddy, Steven J Lye, and Craig E Pennell
dc.identifier.citationJournal of Gastroenterology and Hepatology, 2012; 27(9):1520-1527
dc.identifier.doi10.1111/j.1440-1746.2012.07120.x
dc.identifier.issn0815-9319
dc.identifier.issn1440-1746
dc.identifier.orcidPalmer, L. [0000-0002-1628-3055]
dc.identifier.urihttp://hdl.handle.net/2440/86364
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/353514
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/403981
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/572613
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/634445
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/404166
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/513761
dc.rights© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
dc.source.urihttps://doi.org/10.1111/j.1440-1746.2012.07120.x
dc.subjectAdolescents; non-alcoholic fatty liver disease; raine cohort
dc.titleCholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity
dc.typeJournal article
pubs.publication-statusPublished

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