Association of the Glu298Asp polymorphism in the endothelial nitric oxide synthase gene with essential hypertension resistant to conventional therapy

被引:106
作者
Jáchymová, M
Horky, K
Bultas, J
Kozich, V
Jindra, A
Peleska, J
Martásek, P
机构
[1] Charles Univ Prague, Fac Med 1, Dept Pediat, Prague 12901 2, Czech Republic
[2] Charles Univ Prague, Fac Med 1, Dept Med 2, Prague 12901 2, Czech Republic
[3] Charles Univ Prague, Fac Med 1, Dept Inherited Metab Disorders, Prague 12901 2, Czech Republic
关键词
endothelial nitric oxide synthase; eNOS polymorphism; eNOS gene Glu298Asp variant; eNOS exon seven 894G to T polymorphism; essential hypertension;
D O I
10.1006/bbrc.2001.5007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) which, after diffusing into vascular smooth muscle cells, activates guanylate cyclase leading to vasodilatation. A polymorphism (894G to T) in exon 7 of the eNOS gene causes the conversion of Glu to Asp in position 298. The recently described crystal structure of the heme domain of eNOS protein shows that Glu298 is fully solvent accessible and distant from regions integral to enzyme function. Searching for phenotypic expression of eNOS gene variants, we genotyped a group of patients with essential hypertension (H, n = 119) for the Glu298Asp polymorphism and compared them with age-and sex-matched healthy normals (N, n = 85). To specify phenotypic expression further, the hypertensive patients were subdivided into one group that responded well to regular antihypertensive therapy (CH, n = 45) and one group that was resistant to the therapy (RH, n = 74). Patients with BP higher than 149/90 mmHg when on adequate lifestyle modification and triple-combination therapy (including diuretics) were considered resistant. In RH and H groups, a significantly higher frequency of T alleles (P = 0.022 and P = 0.046, respectively) was found compared to normotonics (N). In well-controlled hypertonics, the same tendency was found, but did not reach statistical significance. The Glu298Asp polymorphism may contribute to the complex pathogenesis of essential hypertension and may be a factor in the resistance of these patients to conventional antihypertensive therapy. The presence of this allele may thus be predictive of the patients' therapeutic response. (C) 2001 Academic Press.
引用
收藏
页码:426 / 430
页数:5
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