Combination of polymorphisms in the beta2-adrenergic receptor and nitric oxide synthase 3 genes increases the risk for hypertension.
OBJECTIVE
Hypertension is a major risk factor for cardiovascular disease. Polymorphism in the beta2-adrenergic receptor (ADRB2) and nitric oxide synthase 3 (NOS3) genes is associated with clinical cardiovascular phenotypes. The Arg16Gly and Glu298Asp polymorphisms of ADRB2 and NOS3 genes, respectively, have been reported to be associated with hypertension. We hypothesized that a combination of these two polymorphisms increases the risk for hypertension. Hence, we examined the effect of this combination of single-nucleotide polymorphisms on the risk for hypertension.


METHODS
Our cross-sectional study comprised 402 middle-aged and elderly human participants. We determined the genotypes of Arg16Gly and Glu298Asp single-nucleotide polymorphisms in ADRB2 and NOS3, respectively, by TaqMan PCR method; we also measured the resting blood pressure.


RESULTS
The odds ratio for the presence of hypertension in individuals having the Gly/Gly genotype of ADRB2 compared with those having the other genotypes (Arg/Arg and Arg/Gly) was 2.87. With regard to the Glu298Asp polymorphism in NOS3, the odds ratio for the presence of hypertension in individuals having the Glu/Glu genotype of NOS3 when compared with those having the other genotypes (Asp/Asp and Asp/Glu) was 2.79. Interestingly, the odds ratio was 7.64 for individuals having a combination of the Gly/Gly genotype of ADRB2 and Glu/Glu genotype of NOS3 when compared with those having a combination of Arg/Arg and Arg/Gly genotypes of ADRB2 and Asp/Asp and Asp/Glu genotypes of NOS3.


CONCLUSIONS
We revealed that a combination of the Arg16Gly and Glu298Asp polymorphisms in ADRB2 and NOS3, respectively, remarkably increased the risk for hypertension in middle-aged and elderly humans.
Division of Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Maiko
M
Misono
Seiji
S
Maeda
Motoyuki
M
Iemitsu
Yoshio
Y
Nakata
Takeshi
T
Otsuki
Jun
J
Sugawara
Hirofumi
H
Zempo
Mutsuko
M
Yoshizawa
Asako
A
Miyaki
Shinya
S
Kuno
Mitsuo
M
Matsuda
Ryuichi
R
Ajisaka
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D017931:DNA Primers; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D017931:DNA Primers; D018343:Receptors, Adrenergic, beta-2; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III