Journal article
Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity
Journal of Gastroenterology and Hepatology, Vol.27(9), pp.1520-1527
2012
Abstract
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.
Details
- Title
- Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity
- Authors/Creators
- L.A. Adams (Author/Creator) - Sir Charles Gairdner HospitalJ.A. Marsh (Author/Creator) - Department of Primary Industries and Regional DevelopmentO.T. Ayonrinde (Author/Creator) - The University of Western AustraliaJ.K. Olynyk (Author/Creator) - The University of Western AustraliaW.Q. Ang (Author/Creator) - Department of Primary Industries and Regional DevelopmentL.J. Beilin (Author/Creator) - The University of Western AustraliaT. Mori (Author/Creator) - The University of Western AustraliaL.J. Palmer (Author/Creator) - Ontario Institute for Cancer ResearchW.W. Oddy (Author/Creator) - The Kids Research Institute AustraliaS.J. Lye (Author/Creator) - Lunenfeld-Tanenbaum Research InstituteC.E. Pennell (Author/Creator) - The Kids Research Institute Australia
- Publication Details
- Journal of Gastroenterology and Hepatology, Vol.27(9), pp.1520-1527
- Publisher
- Wiley-Blackwell
- Identifiers
- 991005540003407891
- Copyright
- © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.663 NAFLD
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine