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Association between 894G>T Polymorphism in the Endothelial Nitric Oxide Synthase Gene and Circadian Variation of Blood Pressure in Patients with Essential Hypertension

內皮細胞一氧化氮合成酶之894G>T多型態與原發性高血壓患者晝夜血壓變化之相關性

摘要


Background: Human essential hypertension has a genetic basis, and hypertension is associated with altered endothelial nitric oxide (NO) release. We hypothesized that functional alterations of the endothelium-derived NO pathway in the presence of the 894G>T polymorphism of the endothelial NO synthase (eNOS) gene may be related to circadian variation of blood pressure in patients with essential hypertension. Methods: A total of 101 ambulatory patients (49 men, 52 women) with essential hypertension were recruited in this study. Noninvasive ambulatory blood pressure monitoring and genotyping by polymerase chain reaction amplification of all subjects were performed. The patients were then classified into four groups according to their dipping status: extreme dippers, dippers, non-dippers, and risers. Chi-square test was used for comparison of the allelic and genotypic frequencies among different groups. Results: The frequencies of the genotypic and allelic frequencies in the study population were comparable to previous reports. There was a trend of increase of genotypic and allelic frequencies of the 894G>T polymorphism in the non-dipper group (non-dippers + risers; n=52) as compared to the dipper group (dippers + extreme dippers; n=49), although the difference was not statistically significant. However, a significant increase in the genotypic (p=0.021) frequency and allelic frequency (p=0.028) of the 894G>T variant in the risers (n=8), compared to those of the dippers (n=45) was noted. After adjustment for age, gender, body mass index, diabetes mellitus, hyperlipidemia, and smoking status, the presence of 894G>T variant remained a significant predictor of risers (odds ratio 7.95; 95% C.I.=1.36-46.4; p=0.021). Conclusions: In this study, a significant association of the 894G>T variant with circadian variation of BP in patients with essential hypertension was demonstrated. These findings are clinically relevant and warrant further investigation in a larger study.

並列摘要


Background: Human essential hypertension has a genetic basis, and hypertension is associated with altered endothelial nitric oxide (NO) release. We hypothesized that functional alterations of the endothelium-derived NO pathway in the presence of the 894G>T polymorphism of the endothelial NO synthase (eNOS) gene may be related to circadian variation of blood pressure in patients with essential hypertension. Methods: A total of 101 ambulatory patients (49 men, 52 women) with essential hypertension were recruited in this study. Noninvasive ambulatory blood pressure monitoring and genotyping by polymerase chain reaction amplification of all subjects were performed. The patients were then classified into four groups according to their dipping status: extreme dippers, dippers, non-dippers, and risers. Chi-square test was used for comparison of the allelic and genotypic frequencies among different groups. Results: The frequencies of the genotypic and allelic frequencies in the study population were comparable to previous reports. There was a trend of increase of genotypic and allelic frequencies of the 894G>T polymorphism in the non-dipper group (non-dippers + risers; n=52) as compared to the dipper group (dippers + extreme dippers; n=49), although the difference was not statistically significant. However, a significant increase in the genotypic (p=0.021) frequency and allelic frequency (p=0.028) of the 894G>T variant in the risers (n=8), compared to those of the dippers (n=45) was noted. After adjustment for age, gender, body mass index, diabetes mellitus, hyperlipidemia, and smoking status, the presence of 894G>T variant remained a significant predictor of risers (odds ratio 7.95; 95% C.I.=1.36-46.4; p=0.021). Conclusions: In this study, a significant association of the 894G>T variant with circadian variation of BP in patients with essential hypertension was demonstrated. These findings are clinically relevant and warrant further investigation in a larger study.

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