Associations of the ATP-binding cassette transporter A1 R219K polymorphism with HDL-C level and coronary artery disease risk: a meta-analysis

Objective: Previous studies have evaluated the associations of the ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism (rs2230806) with the level of high-density lipoprotein cholesterol (HDL-C) and the risk of developing coronary artery disease (CAD), but results from many small, underpowered studies are conflicting. The objective of this study was to overcome the limitations of individual study and provide solid epidemiologic evidence.

Methods: We conducted a systematic review and meta-analysis of available studies to clarify the associations of the ABCA1 R219K polymorphism with HDL-C level and CAD risk.

Results: Through retrieving PubMed, Embase, Web of Science, CBM and CNKI, we identified a total of 22 studies with 6597 cases and 15,369 controls for the association between the ABCA1 R219K polymorphism and CAD risk. The carriers of allele 219K were found to have a lower risk of CAD than the non-carriers: OR=0.76, 95% CI=0.68-0.85, P=3.78E-07, P(heterogeneity)=3.59E-08; meanwhile, 18 studies from 17 papers with 12,869 subjects were included in the association between the ABCA1 R219K polymorphism and the level of HDL-C. It was suggested that the carriers of KK genotype had higher level of HDL-C than those of RR genotype: SMD=0.19, 95% CI=0.06-0.32, P=0.005, P(heterogeneity)=3.19E-09. Subgroup analyzes by ethnicity certified that the effect on HDL level was just significant in Asians. Exclusion of the outlier studies effectively removed the heterogeneity and confirmed the total results. No publication bias was detected in this meta-analysis.

Conclusions: The synthesis of available evidence demonstrates that the ABCA1 R219K polymorphism is associated with a higher HDL-C level in Asians and a protective role for CAD risk both in Asians and Caucasians.