Genetic analysis of 22 candidate genes for hypertension in the Japanese population.
OBJECTIVE
We performed association studies between 118 single-nucleotide polymorphisms (SNPs) of 22 candidate genes (or gene family) and hypertension in a Japanese population.


METHODS
The study population consisted of 1880 subjects representing the general population in Japan, recruited from the Suita study. The candidate genes were selected based on their functions, including insulin resistance (APM1, CD36, HSD11B1), oxidative stress (CYBA, GPX1, GSTMs), steroid hormone (ESR1, ESR2, HSD11B2), renal functions (PTGS2, KLK1, NPHS1, NPHS2, SGK, SLC12A1, PTGES), and others related to cardiovascular physiology (GJA4, NOS1, NTRK3, P2RX4, SPP1, ALDH2).


RESULTS
Multiple logistic analyses, with age and body mass index as covariates, indicated that 13 SNPs (eight genes), six SNPs (four genes) and 11 SNPs (four genes) were associated with hypertension (P < 0.05) in the total, male, and female populations, respectively. PTGS2 seems to be a promising candidate gene for hypertension in men. GSTM3 and SLC12A1 seem to be promising candidate genes for hypertension in women. Especially, a polymorphism in SLC12A1 was significantly associated with hypertension in women even after correction by the Bonferroni method (corrected P = 0.0236). Multiple logistic analyses, with age and body mass index as covariates, indicated that the prevalence of hypertension in females was significantly higher in subjects with the CC genotype than in those with the TT + TC genotypes (P < 0.0001, odds ratio = 1.967, 95% confidence interval = 1.430-2.712).


CONCLUSIONS
Although the present results should be replicated in other study populations for confirmation, the present results suggest that SLC12A1 may contribute to hypertension in Japanese women.
Iwai
Naoharu
N
National Cardiovascular Center, Suita, Osaka, Japan. iwai@ri.ncvc.go.jp
Tago
Naomi
N
Yasui
Naomi
N
Kokubo
Yoshihiro
Y
Inamoto
Nozomu
N
Tomoike
Hitonobu
H
Shioji
Keisuke
K
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA