Genetics
Two linked CETP SNPs more than double the odds of fatty liver in adolescent girls, independent of adiposity (J Gastroenterol Hepatol 2012)
Original title: Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity
Genotyping 951 seventeen-year-olds from the Western Australian Pregnancy (Raine) Cohort for 57 SNPs across seven lipid metabolism genes, including CETP, researchers examined associations with fatty liver disease (FLD, prevalence 16.2%, higher in females at 21.2% versus 11.4% in males). In females, two linked CETP SNPs were associated with FLD: rs12447924 (OR 2.16, 95% CI 1.42 to 3.32, P=0.0003) and rs12597002 (OR 2.22, 95% CI 1.46 to 3.41, P=0.0002). Among lean subjects, FLD probability exceeded 30% in homozygotes for the risk variant, compared with 10 to 15% in heterozygotes and 3 to 5% in wild-type carriers, demonstrating that CETP genotype independently raises fatty liver risk in adolescent girls beyond what adiposity alone explains.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.