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 alpha(2C)DEL322-325, beta(1)Gly389Arg, beta(2)Arg16Gly, and beta(2)Gln27Glu 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. Result: The minor alleles were alpha 2cDel322-325, beta(1)Gly389, beta(2)Gly16, and beta(2)Glu27 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, alpha(2C)Del322-325 allele carrier state, and beta(2)Gln27 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), beta(2C)Del322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P =.0003), and beta(2)Gln27 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 beta(2)Gln27 allele was evident only when the a2cDel322-325 allele was absent. Conclusions: The beta(2C)Del322-325 allele carrier state and beta(2)Gln27 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.