Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population--the Suita Study.
BACKGROUND
Reproducibility of results is important for the validity of genetic association studies. Recently, 3 functional polymorphisms, G(-930)A in CYBA, T481S in CLCNKB, and E65K in KCNMB1, were reported to be associated with blood pressure (BP) status and the aim of this study was to confirm those findings using a large cohort representing the general Japanese population.


RESULTS
The study population consisted of 3,652 subjects recruited from the Suita study as representative of the general population in Japan. The genotypes of the 3 polymorphisms were determined by the TaqMan method. Logistic analysis indicated that the CYBA/G(-930)A polymorphism was associated with hypertension in male subjects. In the male population, the odds ratio of the GG genotype over GA + AA was 1.27 (95% confidence interval 1.01-1.57, p=0.034). Moreover, residuals of systolic and diastolic BP values were significantly higher in subjects with the GG genotype than in those with the GA or AA genotype (p=0.0007). However, such significant effects of the genotype on BP status were not observed in the female population. The significance of the CLCNKB/T481S and KCNMB1/E65K polymorphisms were not replicated in the present study.


CONCLUSIONS
The significance of the G(-930)A polymorphism of CYBA was confirmed in the present study with adequate statistical power, which strengthens the hypothesis that this polymorphism is important in the pathogenesis of hypertension and confers susceptibility.
Kokubo
Yoshihiro
Y
National Cardiovascular Center, Suita, Osaka, Japan.
Iwai
Naoharu
N
Tago
Naomi
N
Inamoto
Nozomu
N
Okayama
Akira
A
Yamawaki
Hideyuki
H
Naraba
Hiroaki
H
Tomoike
Hitonobu
H
D000368:Aged; D027321:Anion Transport Proteins / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics*; D012737:Sex Factors
D027321:Anion Transport Proteins; C412733:CLCNKB protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D024681:Potassium Channels, Calcium-Activated; D019255:NADPH Oxidases; C086986:CYBA protein, human