Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina

Background Sympathetic activity mediated by adrenergic receptors (ARs) appears to play an important role in controlling the vasomotor tone and, thus, may be associated with vasospastic angina (VA). We investigated the association of the common functional polymorphisms of the AR gene and VA. The candidates were α2CDel322-325, β1Gly389Arg, β2Arg16Gly, and β2Gln27Glu polymorphisms. Methods Eighty-two patients with VA, confirmed by coronary angiography with or without ergonovine provocation test, and 114 apparently healthy control subjects were investigated for genotype of 4 AR polymorphisms and established risk factors of ischemic heart disease. Results The minor alleles were α2CDel322-325, β1Gly389, β2Gly16, and β2Glu27 and their frequencies were 7%, 18%, 42%, and 29%, respectively, in the control subjects of this Korean population, which were different from those of other ethnic groups. On univariate analysis, age, smoking, male sex, α2CDel322-325 allele carrier state, and β2Gln27 homozygote state were significant risk factors for VA. After multivariate analysis using multiple logistic regression model, age (odds ratio [OR] 1.809, CI 1.046-1.135, P < .0001), smoking (OR 4.902, CI 2.105-11.416, P = .0002), α2CDel322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P = .0003), and β2Gln27 allele homozygosity (OR 3.152, CI 1.364-7.285, P = .0072) remained as independent risk factors. In the combined genotype analysis, the effect of β2Gln27 allele was evident only when the α2CDel322-325 allele was absent. Conclusions The α2CDel322-325 allele carrier state and β2Gln27 allele homozygote state were identified as novel risk factors of VA in this Korean population. This result suggests the importance of the adrenergic stimuli and the genetic background in the pathogenesis of the VA.