Gender specific association of ABCA1 gene R219K variant in coronary disease risk through interactions with serum triglyceride elevation in Turkish adults

Abstract

Objective: ATP binding cassette transporter A1 (ABCA1) controls the reverse cholesterol transport. Some ABCA1 variants are correlated with serum high-density lipoprotein cholesterol (HDL-C) and other lipid concentrations. We aimed to explore the relationship of ABCA1 gene with both the lipid profile and coronary heart disease (CHD) risk. Methods: Selected 627 individuals of the Turkish Adult Risk Factor Study were genotyped for ABCA1 R219K polymorphism using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. Student's t-test, one-way ANOVA, Chi-square test, linear and logistic regression was used for statistical analysis. Results: We demonstrated a gender-specific effect of the R219K polymorphism on plasma lipids and CHD. In men, while homozygosity of the K allele was associated with increased plasma low-density lipoprotein cholesterol (LDL-C) (p<0.05) and total cholesterol concentrations (p<0.05), carriage of this allele was associated with higher HDL-C concentrations (p<0.05) after adjustment for associated risk factors, but not with CHD. In women, however, without being related to HDL-C levels, each 219K allele was associated with 10% higher triglycerides (TG) concentrations (p<0.05). R219K heterozygosity in women independently doubled (95% CI 1.00; 3.80) the odds ratio for CHD risk in regression models, after adjustment for several variables. Interaction of TG elevation (>140 mg/dL) with CHD was demonstrated in female 219RK genotype carriers. Conclusion: R219 allele of the ABCA1 gene independently confers CHD risk in heterozygote Turkish women, not via reduced HDL-C, but interacting with elevated TG expressed by the 219K allele, but not in men. (Anadolu Kardiyol Derg 2014; 14: 18-25)

Functional and Structural Impact of ATP-Binding Cassette Transporter A1 R219K and I883M Gene Polymorphisms in Obese Children and Adolescents

“…Consistent with our results, Villard et al reported R219K SNP to be associated with a significant modification of cholesterol efflux capacity in a sex-dependent manner [53]. Genderspecific differential effect of ABCA1 gene polymorphisms was also observed in coronary disease risk and plasma lipid levels in Turkish adults [54]. These observations could be explained by the fact that sex hormones regulate many genes involved in HDL biogenesis, leading to altered lipid levels in women compared with men [53].…”

“…In healthy-weight subjects, R219K SNP was shown to be associated with altered HDL-c phenotype [65,66]. Homozygotes of the A allele of R219K were associated with increased LDL-C and TC and decreased HDL-c concentrations in Turkish population [54]. Similarly, young Greek women with the GG genotype of the same SNP exhibited lower TC and LDL-c levels compared with the GA genotype [22].…”

Association Between Four ABCA1 gene Polymorphisms and Risk of Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

“…In addition, the increased serum levels of LDL cholesterol were observed in the NAFLD patients with the ABCA1 rs2066714 C allele. The same result was also reported in Turkish adults indicating that the R219K variant (rs2230806 G > A) of ABCA1 was associated with the increased serum LDL cholesterol levels (37). No significant difference in the serum LDL cholesterol levels of NAFLD patients was observed between the carriers and noncarriers of the ABCA1 rs1800977 A, rs2066715 C, and rs2230808 T.…”

Impact of 3 Common ABCA1 Gene Polymorphisms on Optimal vs Non-Optimal Lipid Profile in Greek Young Nurses

“…We examined the impact of the R219K , R1587K and I883M of ABCA1 polymorphisms as a genetic influence on the lipid profile in Greek subjects. In this context, the possible effects of the ABCA1 polymorphisms on lipids or cardiovascular disease were recently evaluated in various populations such as Japanese [ 11 ] in which correlation with HDL-C concentrations was found, Saudi [ 12 ] in which the ABCA1 C69T gene frequency was higher in healthy subjects compared with diabetic patients, Chinese [ 13 ], in which ABCA1 gene R219K polymorphism was associated with ischemic stroke, Greek [ 5 - 7 ] in which a gender-specific effect of the R219K polymorphism on plasma lipids was demonstrated, Turkish [ 14 ] in which a gender-specific effect of the R219K polymorphism on plasma lipids and CHD was shown and Mexican [ 15 ] in which several European loci as well as a novel one for high TG and low HDL-C levels were identified. However, the results are still confusing.…”