Aldosterone synthase gene (CYP11B2) C-334T polymorphism, ambulatory blood pressure and nocturnal decline in blood pressure in the general Japanese population: the Ohasama Study.
OBJECTIVE
The C-344T polymorphism in the 5'-flanking region of the aldosterone synthase (CYP11B2) gene has been suggested to be associated with hypertension and disturbed circadian blood pressure (BP) rhythm through its effect on aldosterone synthesis. However, previous findings on this topic have been inconsistent.


METHODS
A cross-sectional study.


METHODS
We investigated the CYP11B2 C-344T genotype in 802 subjects, aged 40 and over, in a Japanese community, who gave written informed consent and were monitored for 24 h ambulatory BP.


RESULTS
The frequencies of the CC, CT, and TT genotypes in these Japanese subjects were 0.14, 0.44, and 0.42, showing a higher frequency of the T allele (0.64) than in Caucasians. Although there was no significant difference in 24 h ambulatory BP levels among the genotypes, the nocturnal decline in BP was significantly greater in the CC homozygous subjects than in other subjects (P = 0.0065 for systolic and P = 0.031 for diastolic decline in nocturnal BP). Detailed analyses demonstrated that this association was significant only in aged (60 years and over) or male subjects. The prevalence of previous cardiovascular disease was significantly less in these subjects with the CC genotype than in those with the TC and TT genotypes, although age, body mass index, male gender, smoking, use of alcohol and antihypertensive medication did not differ among the three genotypes. There was no significant difference among the three genotypes in biochemical and hormonal parameters.


CONCLUSIONS
Although the C-344 T polymorphism of CYP11B2 did not directly influence the level of 24 h BP, the CC genotype was associated with decreased nocturnal BP in elderly or male Japanese. Since prevalence of previous cardiovascular disease was significantly less in homozygous CC subjects, greater nocturnal BP decline in this genotype appears to be beneficial in the circadian BP rhythm.
Matsubara
M
M
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Medicine and Pharmaceutical Science, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. mmitsu2i@mail.cc.tohoku.ac.jp
Kikuya
M
M
Ohkubo
T
T
Metoki
H
H
Omori
F
F
Fujiwara
T
T
Suzuki
M
M
Michimata
M
M
Hozawa
A
A
Katsuya
T
T
Higaki
J
J
Tsuji
I
I
Araki
T
T
Ogihara
T
T
Satoh
H
H
Hisamichi
S
S
Nagai
K
K
Kitaoka
H
H
Imai
Y
Y
D000368:Aged; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002318:Cardiovascular Diseases / Q000235:genetics; D002940:Circadian Rhythm; D003430:Cross-Sectional Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology
D019405:Cytochrome P-450 CYP11B2