Pal Gopal Krushna, Adithan Chandrasekaran, Umamaheswaran Gurusamy, Pal Pravati, Nanda Nivedita, Indumathy Jagadeeswaran, Syamsunder Avupati Naga
Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
Department of Pharmacology, JIPMER, Puducherry, India.
J Am Soc Hypertens. 2016 Nov;10(11):865-872. doi: 10.1016/j.jash.2016.09.001. Epub 2016 Sep 15.
Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented in the causation of hypertension, its role in prehypertension has not been investigated. The present study was conducted in 172 subjects divided into prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV) parameters including baroreflex sensitivity (BRS) by continuous BP variability assessment and sympathovagal imbalance (SVI) by heart rate variability analysis were recorded. Biochemical parameters for insulin resistance (homeostatic model for assessment of insulin resistance), oxidative stress, lipid risk factors, renin, and inflammatory parameters were measured. Genotyping for eNOS polymorphisms rs1799983 (298G>T) and rs2070744 (-786T>C) was performed by polymerase chain reaction-restriction fragment length polymorphism method. Multiple regression analysis was done to assess the association between SVI and metabolic markers, and multivariate logistic regression was done to determine the prediction of prehypertension status by genotype, BRS, and ratio of low-frequency to high-frequency in these subjects. The BP variability, heart rate variability, and biochemical parameters were significantly altered in prehypertensives. The eNOS polymorphisms were found to be associated with prehypertension. BRS, the marker of SVI, was significantly associated with BP, homeostatic model for assessment of insulin resistance, and tumor necrosis factor alpha in 298GG genotype of prehypertensive population. The eNOS gene polymorphisms appear to be associated with prehypertension. 298G>T and -786T>C contribute to SVI in young prehypertensives attributed by insulin resistance and inflammation. The CV risks were associated with prehypertension status in prehypertensives expressing both 298GG and -786TT genotypes. Association of CV risks with SVI appears to be stronger in prehypertensives expressing GG genotype.
尽管内皮型一氧化氮合酶（eNOS）基因多态性与高血压的发病有关，但其在高血压前期中的作用尚未得到研究。本研究对172名受试者进行，分为高血压前期组（n = 57）和血压正常组（n = 115）。记录心血管（CV）参数，包括通过连续血压变异性评估的压力反射敏感性（BRS）和通过心率变异性分析的交感迷走失衡（SVI）。测量胰岛素抵抗（胰岛素抵抗评估稳态模型）、氧化应激、脂质风险因素、肾素和炎症参数的生化指标。采用聚合酶链反应-限制性片段长度多态性方法对eNOS基因多态性rs1799983（298G>T）和rs2070744（-786T>C）进行基因分型。进行多元回归分析以评估SVI与代谢标志物之间的关联，并进行多因素逻辑回归以确定这些受试者中基因型、BRS以及低频与高频比值对高血压前期状态的预测。高血压前期患者的血压变异性、心率变异性和生化指标有显著改变。发现eNOS基因多态性与高血压前期有关。在高血压前期人群的298GG基因型中，SVI的标志物BRS与血压、胰岛素抵抗评估稳态模型以及肿瘤坏死因子α显著相关。eNOS基因多态性似乎与高血压前期有关。298G>T和-786T>C通过胰岛素抵抗和炎症导致年轻高血压前期患者的SVI。在同时表达298GG和-786TT基因型的高血压前期患者中，CV风险与高血压前期状态相关。在表达GG基因型的高血压前期患者中，CV风险与SVI的关联似乎更强。
