Genetic variations at ABCG5/G8 genes modulate plasma lipids concentrations in patients with familial hypercholesterolemia

Abstract

Objective: To investigate the association of four common single nucleotide polymorphisms (SNPs) at ABCG5 (i7892A>G, i18429C>T, Gln604GluC>G, i11836G>A) and five at ABCG8 (5U145T>G, Tyr54CysA>G, Asp19HisG>C, i14222T>C, and Thr400LysG>T) with plasma lipids concentrations and to explore the interaction between those SNPs and smoking in patients with FH.

Methods and results: ABCG5/G8 SNPs were genotyped in 500 subjects with genetic diagnosis of FH. Carriers of the minor A allele at the ABCG5_i11836G>A SNP displayed significantly higher HDL-C concentrations (P=0.023) than G/G subjects. In addition, carriers of the minor G allele at the ABCG5_Gln604GluC>G SNP had significantly lower VLDL-C (P=0.011) and lower TG (P=0.017) concentrations than homozygous C/C. Interestingly, a significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5 (i7892A>G, i18429C>T, i11836G>A) SNPs displayed significantly lower HDL-C, higher TC and higher TG respectively, only in smokers. On the other hand, nonsmokers carriers of the minor alleles at ABCG5 (i18429C>T and Gln604GluC>G) SNPs had significantly lower TG concentrations (P=0.012 and P=0.035) compared with homozygous for the major allele.

Conclusions: Our data support the notion that ABCG5/G8 genetic variants modulate plasma lipids concentrations in patients with FH and confirm that this effect could be influenced by smoking. Therefore, these results suggest that gene-environmental interactions can affect the clinical phenotype of FH.

Conflict of interest statement

DISCLOSURES

None of the authors had any conflict of interest.

Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

Association of the ABCG5 SNPs with fasting plasma lipids. Values are mean ± standard error. P values were adjusted for age, gender, BMI, physical activity, diabetes, HTA, smoking habits, lipid lowering drugs and CVD. Figure 1A)ABCG5_i11836 (HDL-C; P=0.023) Figure 1B)ABCG5_Q604E (TG; P=0.017)

Figure 2

Interaction between ABCG5 SNPs and smoking on lipid levels. Values are mean ± standard error. P values were adjusted for age, gender, BMI, physical activity, diabetes, HTA, lipid lowering drugs and CVD Figure 2A) Interaction ABCG5_ i7892-smoking for HDL-C Figure 2B) Interaction ABCG5_i11836-smoking for TG Figure 2C) Interaction ABCG5_i18429-smoking for TG Figure 2D) Interaction ABCG5_Gln604Glu-smoking for TG