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Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension
Open accessAbstract
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.
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Hypertension in mice lacking the gene for endothelial nitric oxide synthase
Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., & Fishman, M. C. (1995) · Nature · doi:10.1038/377239a0 · Cited by 2,070
Lifton, R. P., Dluhy, R. G., Powers, M., Rich, G. M., Cook, S., Ulick, S., & Lalouel, J.-M. (1992) · Nature · doi:10.1038/355262a0 · Cited by 1,158
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Brosius, F. C., Alpers, C. E., Bottinger, E. P., Breyer, M. D., Coffman, T. M., Gurley, S. B., Harris, R. C., Kakoki, M., Kretzler, M., Leiter, E. H., et al. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009070721 · Cited by 895
Self-citationThe role of nitric oxide in cardiovascular diseases
NASEEM, K. (2005) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.09.003 · Cited by 557
Duplain, H., Burcelin, R., Sartori, C., Cook, S., Egli, M., Lepori, M., Vollenweider, P., Pedrazzini, T., Nicod, P., Thorens, B., et al. (2001) · Circulation · doi:10.1161/01.cir.104.3.342 · Cited by 533
Tesauro, M., Thompson, W. C., Rogliani, P., Qi, L., Chaudhary, P. P., & Moss, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2832 · Cited by 527
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Metadata
- Authors
- Miyamoto, Y., Saito, Y., Kajiyama, N., Yoshimura, M., Shimasaki, Y., Nakayama, M., Kamitani, S., Harada, M., Ishikawa, M., Kuwahara, K., Ogawa, E., Hamanaka, I., Takahashi, N., Kaneshige, T., Teraoka, H., Akamizu, T., Azuma, N., Yoshimasa, Y., Yoshimasa, T., Itoh, H., Masuda, I., Yasue, H., & Nakao, K.
- Venue
- Hypertension
- Published
- 1998-07
- Volume
- 32
- Issue
- 1
- Pages
- 3-8
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2141719916
- Cited by
- 519
- References
- 2
- FWCI
- 15.17
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Miyamoto, Y., Saito, Y., Kajiyama, N., Yoshimura, M., Shimasaki, Y., Nakayama, M., Kamitani, S., Harada, M., Ishikawa, M., Kuwahara, K., Ogawa, E., Hamanaka, I., Takahashi, N., Kaneshige, T., Teraoka, H., Akamizu, T., Azuma, N., Yoshimasa, Y., Yoshimasa, T., . . . Nakao, K. (1998). Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension. Hypertension. https://doi.org/10.1161/01.hyp.32.1.3
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