Effects of the polymorphisms in ABCG1 gene on the transcription activity and the susceptibility with coronary artery disease.

Abstract

Objective To investigate the effects of the polymorphisms in the promoter of ATP binding cassette transporter (ABCG1) on the transcription activity, and the relationship of the polymorphisms with the susceptibility to coronary artery disease (CAD). Methods A case-control study was conducted, 217 CADpatients and 142 controls were enrolled in this study.Thesingle nucleotide polymorphisms (SNPs) in the promoter of ABCG1 were identified by sequencing.The promoter haplotypes of ABCG1 were determined with allele specific primer sequencing or Gene cloning sequencing.The transcription activity of the promoter haplotypes were evaluated with dual luciferase reporter system.The frequency of SNPs and haplotypes were analyzed between CAD group and the control group, premature CAD and non-premature CAD group, as well as multivessel lesion and single vessel lesion group. The frequency distribution was compared between two groups with χ2 test or Fisher exact test. The difference of the luciferase activity was compared between groups by t-test or one-way analysis of variance. Results Only 3 SNPs were found in ABCG1 promoter sequence of about 1 000 bp upstream of the transcription start site, which are -384(A/G), -204(A/C) and -134(T/G), respectively.The 3 SNPs are in strong linkage disequilibrium, Tajima’s D = 2.655 (P<0.01), which constituted 3 haplotypes. There was no significant difference in SNPs and haplotype frequency between the CAD group and the normal control group, and the severity of vascular disease and the early onset of coronary heart disease were not associated with the polymorphisms in ABCG1 promoter.There was no significant difference in the transcriptional activity of the three constitutive promoter haplotypes, but the transcriptional activity was notably elevated as the GAT haplotype was mutated into GAG (P<0.05). Conclusions The 3 SNPs identified in ABCG1 promoter region A did not alter the promoter activity.There was no significant correlation between the frequency distribution of SNPs and promoter haplotypes and the susceptibility to CAD. Key words: Coronary atherosclerotic disease; ATP binding cassette transporter G1; Promoter; Single nucleotide polymorphisms; Haplotype; Linkage disequilibrium; Gene cloning; Dual luciferase reporter system