| BACKGROUND AND OBJECT: Blood pressure is a quantitative multifactorial trait influenced by environmental and genetic determinants. Endothelial nitric oxide synthase (eNOs) produces nitric oxide (NO) which, after diffusing into vascular smooth muscle cells, activates guanylate cyclase leading to vasodilatation. eNOs is a potent regulator of vasomotor tone and peripheral vascular resistance. The potent vasodilator property of NO in the resistant arteries, coupled with the genetic basis of hypertension, suggests that mutations affecting the endothelial NO (eNOs) gene, and consequently impairing NO synthesize, might contribute to increased vascular resistance and in turn an elevation in systemic blood pressure (BP). 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 production metabolism is implicated in hypertension. The G-to-T conversion at nucleotide 894 in the eNOs gene, which introduces an aspartic acid in place of a glutamic acid residue (Glu298Asp), is associated with an increased risk for myocardial infarction. A role for eNOs in onset of essential hypertension ( EH ) is, however, controversial. Significant association between the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOs) gene and essential hypertension was reported in a Japanese populations, with the 298Asp variant showing a higher prevalence in hypertensive patients than in normotensive subjects . In contrast, another study demonstrated that the 298Glu variant was significantly associated with hypertension in a Caucasian population. Resently, some studies did not support the previous observation that the molecular variant of the eNOs gene plays a important role in the onset of esential hypertension.In China a study show positive association between the Glu298Asp polymorphism of the NO producing gene and hypertension in old people. Thus we conducted a case-control study of a relatively large size to clarify the uncertain picture about the association of the Glu298Asp polymorphism of the eNOs gene with EH. METHODS: 277 patients with essential hypertension were selected from the outpatient clinics at the second affiliated hospital of Dalian medical university. All patients with essential hypertension were selected according to WHO criteria or having been on antihypertensive therapy. A group of 547 normotensive control subjects were selected from the same clinics whose systolic/diastolic blood pressures<140/90mmHg and absence of antihypertensive treatment. All subjects were excluded secondary hypertension and have been living in the city of DaLian at least ten years. Subjects with a history of diabetes mellitus, coronary artery disease and renal failure were excluded from the present study. Blood was collected at the time of screening for genotyping and for total cholesterol triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C). 109 patients was examined by Ultrasonography and the thickness of interventricular septum (IVS) and LV post wall(IVPW) were measured. The weight and height of the subjects were obtained. The information about smoking, alcohol intake and family history of hypertension was also obtained. Genomic DNA was extracted from 3ml of whole blood by standard methods. The eNOs Glu298As polymorphism was detected by using polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) analysis. All values were expressed as mean ± SD unless otherwise indicated. Statistical significance was defined as P<0.05. The SPSS 11.5 for windows was used in all statisical analysis. The Pearsonχ2 statistics were calculated between genotype distribution (or allele frequencies) and hypertension status. One-way ANOVA was used to compare continuous variables between the two groups. Confounding influences of age, sex, family history of hypertension, TC, TG and BMI were assessed in a multiple l...
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