Association of ADRβ2 Haplotypes with Coronary Artery Disease in Korean Patients

ABSTRACT

BACKGROUND: Beta₂-adrenergic receptor (ADRβ2) gene variations seem to be correlated with disease progression, prognosis, and drug response to β-blockers in cardiovascular events. In this study, we investigated the genotypes and haplotypes of ADRβ2 in Korean patients and analysed their association with coronary artery disease (CAD). METHODS: One hundred five patients diagnosed with stable angina (SA), 109 patients with acute coronary syndrome (ACS), and 88 controls were enrolled. Five single nucleotide polymorphisms (SNPs) were determined at positions 46, 79, 252, 491, and 523 nucleotides, using the polymerase chain reaction and direct sequencing analysis. The haplotype reconstruction was carried out using genotype data, and analyses of the association between the genetic variation and CAD were performed. RESULTS: There were significant differences in the allele frequencies for the 79CG SNPs among the three groups. Relative to the control group, the distribution of 79CG genotypes was significantly different in both the SA group (P=0.0003) and the ACS group (P=0.0056). Compared with the CC genotype of 79CG, subjects with CG or GG had a higher risk of CAD (adjusted odds ratio [OR], 12.851; P=0.014). The frequencies of specific ACGCA, GCACC, and GGGCC haplotypes were 6.4% vs. 0%, 8.3% vs. 0%, and 6.9% vs. 0.6%, respectively, in the ACS group and controls. The GGGCC haplotype was significantly associated with CAD (adjusted OR, 12.266; P=0.016). CONCLUSIONS: Although there are large ethnic differences in the distribution of ADRβ2 SNPs and their association with CAD, the 79G polymorphism and GGGCC haplotype in ADRβ2 might specifically contribute to CAD pathogenesis in Korean patients.