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

journal contribution
posted on 2023-05-18, 19:11 authored by Adams, LA, Marsh, JA, Ayonrinde, OT, Olynyk, JK, Ang, WQ, Beilin, LJ, Mori, T, Palmer, LJ, Wendy OddyWendy Oddy, Lye, SJ, Pennell, CE
BACKGROUND AND AIM: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

History

Publication title

Journal of Gastroenterology and Hepatology

Volume

27

Issue

9

Pagination

1520-1527

ISSN

0815-9319

Department/School

Menzies Institute for Medical Research

Publisher

Blackwell Publishing Asia

Place of publication

54 University St, P O Box 378, Carlton, Australia, Victoria, 3053

Repository Status

  • Restricted

Socio-economic Objectives

Preventive medicine

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    University Of Tasmania

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