Association of (pro)renin receptor gene polymorphism with blood pressure in Japanese men: the Ohasama study.
BACKGROUND
Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin-angiotensin system (RAS), is associated with blood pressure regulation in animals. However, there is no information on (P)RR in humans. We investigated the association of (P)RR gene polymorphisms with blood pressure in a Japanese population.


METHODS
Subjects (n = 1,112) were recruited from participants in the Ohasama study, a Japanese cohort study. For the association study, we selected three polymorphisms: -782A>G (rs2968915), intervening sequence (IVS)5+169C>T (rs5918007), and +1513A>G (rs6609080). Because the (P)RR gene is on the X chromosome, men (n = 357) and women (n = 755) were analyzed separately.


RESULTS
In men, 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) values, daytime SBP and DBP values, and nighttime SBP and DBP values were significantly higher in IVS5+169T allele carriers than C allele carriers. Multiple regression analysis showed that IVS5+169C>T was significantly and independently related to ambulatory blood pressure (ABP). IVS5+169C>T was not associated with casual blood pressure (CBP) in men. In women, there were no significant differences in blood pressure values among the three genotypes of IVS5+169C>T. This polymorphism had no significant association with any other clinical characteristic. -782A>G was weakly associated with ABP in men. +1513A>G was not associated with blood pressure values in either men or women.


CONCLUSIONS
We demonstrated for the first time that polymorphism of the (P)RR gene IVS5+169C>T is associated with ABP in Japanese men. This association suggests that (P)RR has a role in blood pressure regulation.
Hirose
Takuo
T
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, Japan. hirose-t@m.tains.tohoku.ac.jp
Hashimoto
Masahiro
M
Totsune
Kazuhito
K
Metoki
Hirohito
H
Asayama
Kei
K
Kikuya
Masahiro
M
Sugimoto
Ken
K
Katsuya
Tomohiro
T
Ohkubo
Takayoshi
T
Hashimoto
Junichiro
J
Rakugi
Hiromi
H
Takahashi
Kazuhiro
K
Imai
Yutaka
Y
D000368:Aged; D000483:Alleles; D015415:Biomarkers; D001794:Blood Pressure / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D012044:Regression Analysis; D012737:Sex Factors; D000093342:Prorenin Receptor
D015415:Biomarkers; D011956:Receptors, Cell Surface; D004247:DNA; D000093342:Prorenin Receptor