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Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity.
- Source :
-
Journal of Gastroenterology & Hepatology . Sep2012, Vol. 27 Issue 9, p1520-1527. 8p. 4 Charts, 1 Graph. - Publication Year :
- 2012
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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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08159319
- Volume :
- 27
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Gastroenterology & Hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 79242736
- Full Text :
- https://doi.org/10.1111/j.1440-1746.2012.07120.x