Gender Specific Association of ABCA1 Gene R219K Variant in Coronary Disease Risk Through Interactions with Serum Triglyceride Elevation in Turkish Adults

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.