Genetic variations in ABCA1/G1 associated with plasma lipid levels and risk of ischemic stroke

[Display omitted] •ABCA1 SNP rs4149338 and ABCG1 SNP rs57137919 were strongly associated with the risk of IS.•The mRNA expression of ABCG1 was higher in IS group and was associated with low LDL-C level.•Haplotype A-A (rs4149339-rs4149338) was in strong linkage disequilibrium and associated with decreased risk of IS. ATP binding cassette transporters ABCA1 and ABCG1 play a crucial role in cholesterol efflux and reverse cholesterol transport (RCT), thereby rendering ischemic stroke (IS) susceptibility. Variants of ABCA1/G1 have been implicated in etiology of IS. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of ABCA1/G1 with plasma lipid variability and the risk of IS in Chinese Han Population. Totally 249 IS patients and 226 healthy controls were enrolled and 10 SNPs of ABCA1/G1 were screened for genotyping by kompetitive allele-specific polymerase chain reaction (KASP) and validated by sanger sequencing. The logistic regression analysis was performed to identify risk alleles of IS and appropriate genetic model. The genetic risk scores (GRS) and predicted risks for all individuals was computed. Based on different plasma lipid levels, we applied stratified analyses for subgroups. Linkage disequilibrium (LD) test was used to explore different functional haplotype combinations. Association between specific allele or genotype of the SNPs of ABCA1/G1 and plasma lipid or lipoproteins levels were also investigated. Besides total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), significant differences of clinical data were observed between IS and control group. The rare GG genotype frequencies of rs4149338 on ABCA1 was higher in IS patients than those in controls (11.4%, 4.6%, respectively, P = 0.037). Frequencies of rs57137919 on ABCG1 for rare AA genotype was lower in IS group than those in control group (4.6%, 13.3%, respectively, P = 0.030). GRS showed ability to discriminate IS patients and controls (AUC = 0.633, P