title: Paraoxonase gene Gln192Arg (Q192R) polymorphism is associated with coronary artery spasm.
abstract: We recently reported that oxidative stress is involved in the pathogenesis of coronary spasm. We hypothesized that oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase gene (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) might influence the pathogenesis of coronary spasm. We therefore examined the possible association between the PON1 Q192R or PAF-AH V279F polymorphisms and coronary spasm in 214 patients with coronary spasm and 212 control subjects. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. The incidence of the PON1-192R allele was significantly higher in the coronary spasm group than in the control group (65% vs 53%; P=0.0005). The PAF-AH-279F allele was not associated with coronary spasm (15% vs. 16%; P=0.8781). Multiple logistic regression analysis with forward stepwise selection involving the PON1-192R allele and the environmental risk factors revealed that the most predictive independent risk factor for coronary spasm was the PON1-192R allele (significance=0.0016, OR=2.52), followed by cigarette smoking (significance=0.0007, OR=2.01). We also measured plasma levels of TBARS (thiobarbituric acid-reactive substances) as a marker of oxidative stress. TBARS levels were higher in R/R types than in Q/Q types (2.115+/-0.086 nmol/ml [ n=25] vs 1.676+/-0.102 nmol/ml [ n=11], P<0.01). Thus, there is a significant association between the PON1-192R allele and coronary spasm; the PON1-192R allele may play an important role in the genesis of coronary spasm, probably by attenuating the suppression of oxidative stress.
authors.affiliation: Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Ito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasue
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Shimasaki
authors.forename: Eisaku
authors.initials: E
authors.lastname: Harada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawano
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001120:Arginine; D043303:Aryldialkylphosphatase; D002784:Cholesterol / Q000097:blood; D003329:Coronary Vasospasm / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D048909:Diabetes Complications; D004950:Esterases / Q000235:genetics*; D005260:Female; D005838:Genotype; D005973:Glutamine; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012907:Smoking; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D005973:Glutamine; D001120:Arginine; D002784:Cholesterol; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human