Abstract
Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n = 458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P<0.0017; Kumamoto: 0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.
| Original language | English |
|---|---|
| Pages (from-to) | 3-8 |
| Number of pages | 6 |
| Journal | Hypertension |
| Volume | 32 |
| Issue number | 1 |
| Publication status | Published - 1998 Jul |
| Externally published | Yes |
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Keywords
- Genes
- Genetics
- Hypertension, essential
- Nitric oxide synthase
- Polymorphism
ASJC Scopus subject areas
- Internal Medicine
Cite this
Endothelial nitric oxide synthase gene is positively associated with essential hypertension. / Miyamoto, Yoshihiro; Saito, Yoshihiko; Kajiyama, Noboru; Yoshimura, Michihiro; Shimasaki, Yukio; Nakayama, Masafumi; Kamitani, Shigeki; Harada, Masaki; Ishikawa, Masahiro; Kuwahara, Koichiro; Ogawa, Emiko; Hamanaka, Ichiro; Takahashi, Nobuki; Kaneshige, Toshihiko; Teraoka, Hiroshi; Akamizu, Takashi; Azuma, Nobuyuki; Yoshimasa, Yasunao; Yoshimasa, Takaaki; Itoh, Hiroshi; Masuda, Izuru; Yasue, Hirofumi; Nakao, Kazuwa.
In: Hypertension, Vol. 32, No. 1, 07.1998, p. 3-8.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelial nitric oxide synthase gene is positively associated with essential hypertension
AU - Miyamoto, Yoshihiro
AU - Saito, Yoshihiko
AU - Kajiyama, Noboru
AU - Yoshimura, Michihiro
AU - Shimasaki, Yukio
AU - Nakayama, Masafumi
AU - Kamitani, Shigeki
AU - Harada, Masaki
AU - Ishikawa, Masahiro
AU - Kuwahara, Koichiro
AU - Ogawa, Emiko
AU - Hamanaka, Ichiro
AU - Takahashi, Nobuki
AU - Kaneshige, Toshihiko
AU - Teraoka, Hiroshi
AU - Akamizu, Takashi
AU - Azuma, Nobuyuki
AU - Yoshimasa, Yasunao
AU - Yoshimasa, Takaaki
AU - Itoh, Hiroshi
AU - Masuda, Izuru
AU - Yasue, Hirofumi
AU - Nakao, Kazuwa
PY - 1998/7
Y1 - 1998/7
N2 - Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n = 458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P<0.0017; Kumamoto: 0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.
AB - Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n = 458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P<0.0017; Kumamoto: 0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.
KW - Genes
KW - Genetics
KW - Hypertension, essential
KW - Nitric oxide synthase
KW - Polymorphism
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UR - http://www.scopus.com/inward/citedby.url?scp=0031902667&partnerID=8YFLogxK
M3 - Article
C2 - 9674630
AN - SCOPUS:0031902667
VL - 32
SP - 3
EP - 8
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 1
ER -