ABCG5/8 variants are associated with susceptibility to coronary heart disease

Abstract

ATP-binding cassette sub-family G member 5 (ABCG5) and ABCG8 are members of an ATP-binding cassette transporter superfamily. ABCG5 and ABCG8 variants affected serum levels of cholesterol and were considered as risk factors for coronary heart disease (CHD). The present control study analyzed ABCG5 and ABCG8 variants in a population for association with the risk of CHD. A total of 417 CHD patients and 267 controls were recruited for genotyping of four single nucleotide polymorphisms (SNPs; i.e. i7892T>C in ABCG5 and Tyr54CysA>G, Thr400LysC>A and 5U145A>C in ABCG8) using quantitative PCR high-resolution melting (qPCR-HRM). Serum lipid levels were measured using an automatic biochemical analyzer. The association of ABCG5/8 variants with lipid levels was analyzed using a Chi-square test. The impact of candidate ABCG5/8 SNPs on CHD was evaluated in a dominant genetic model with stepwise multiple regression analysis. Subgroup analyses were performed with regard to these SNPs, tobacco smoking status, alcohol consumption and gender. Genotypic and allelic frequencies of ABCG8 Thr400LysC>A were significantly different (P<0.05) between CHD patients and controls. CC homozygotes of the ABCG8 Thr400LysC>A SNP had greater triglyceride levels than CA/AA carriers with CHD. Logistic analysis revealed CHD risk was significantly higher in CC homozygotes of ABCG8 Thr400LysC>A than in carriers of the A allele (adjusted P=0.048; OR=2.034; 95% CI=0.983-4.207). Furthermore, there was a significant gene-tobacco smoking interaction. CC homozygotes of ABCG8 Thr400LysC>A SNP had significantly higher triglyceride concentrations (P=0.012) and an increased risk of CHD than tobacco smoking carriers of the A allele. The data from the current study suggested that ABCG8 Thr400LysC>A SNP genetic variants modulated plasma triglyceride levels and thereby affected CHD risk in the population studied. The genetic variant of ABCG8 also contributed to CHD risk through interaction with tobacco smoking.

Lack of an association between matrix metalloproteinase polymorphisms and coronary heart disease in a Han Chinese population

“…CHD is a complex disease, involving interactions between environmental and genetic factors (Feng et al, 2014). Previous studies have found that single nucleotide polymorphisms (SNPs), important genomic elements, can affect an individual's genetic susceptibility to various diseases, including CHD Muiya et al, 2014;Wu et al, 2014;Yang et al, 2014).…”

Case Report: Next Generation Sequencing in Clinical Practice–A Real Tool for Ending the Protracted Diagnostic Odyssey

“…They demonstrated that individuals carrying the risk genotype for both ABCG8 variants had an increased risk of cardiovascular disease (RR 1.57, 95% CI 1.13–2.18; p = 0.01) and coronary heart disease (RR 1.72, 95% CI 1.23–2.41; p = 0.002). Wu et al ( 41 ) investigated the association between four ABCG5 and ABCG8 SNPs and CAD. Binary logistic regression analysis demonstrated that the homozygous C allele at Thr400LysC>A (rs4148217) resulted in a more than 2-fold greater risk of developing CAD, compared with those who carried the A allele in a dominant model.…”

Genetic association studies using disease liabilities from deep neural networks

“…ABCG8 (ATP-binding cassette subfamily G member 8) is an instance of a new susceptibility gene for angina pectoris identified by our combined approach. It has been previously reported that ABCG8 variants are risk factors for coronary heart disease 23 . ZC3H4 (zinc finger CCCH domain-containing protein 4) is a candidate gene associated with susceptibility to type 2 diabetes (T2D) identified via the combined approach alone.…”