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 alpha2CDel322-325, beta1Gly389Arg, beta2Arg16Gly, and beta2Gln27Glu 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 alpha2CDel322-325, beta1Gly389, beta2Gly16, and beta2Glu27 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, alpha2CDel322-325 allele carrier state, and beta2Gln27 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), alpha2CDel322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P = .0003), and beta2Gln27 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 beta2Gln27 allele was evident only when the alpha2CDel322-325 allele was absent.


CONCLUSIONS
The alpha2CDel322-325 allele carrier state and beta2Gln27 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.
Cardiovascular Research Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Jin-Shik
JS
Park
Shu-Ying
SY
Zhang
Sang-Ho
SH
Jo
Jae-Bin
JB
Seo
Lian
L
Li
Kyung-Woo
KW
Park
Byung-Hee
BH
Oh
Young-Bae
YB
Park
Hyo-Soo
HS
Kim
D000328:Adult; D000483:Alleles; D000788:Angina Pectoris, Variant / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011941:Receptors, Adrenergic / Q000235:genetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
C547774:ADRA2C protein, human; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2