Association between endothelial nitric oxide synthase and the renin-angiotensin-aldosterone system polymorphisms, blood pressure and training status in normotensive/pre-hypertension and hypertensive older adults: a pilot study

<b>Introduction:</b>Variations in blood pressure (BP) are, in part, genetically determined and some polymorphisms of renin-angiotensin- aldosterone system (RAAS) and synthase of endothelial nitric oxide (eNOS) have been related to hypertension (HT). Conversely, physical exercise is considered a non-pharmacological tool for HT control, treatment, and prevention. <b>Objective:</b> The purpose of this study is to investigate the relationship between eNOS and RAAS polymorphisms, their epistatic interaction, and the respective humoral factors in the BP control in normotensive/pre-hypertension and hypertensive older adults and how this relationship can be modulated by training status (TS) level. <b>Methods:</b>A total of 155 older adults (66.94 ± 6.83 years old) performed the following evaluations: AAHPERD battery test to determine the general functional fitness index (GFFI), systolic and diastolic blood pressure (SBP and DBP), blood collection for DNA extraction, analysis of eNOS gene polymorphisms rs2070744; rs61722009 and rs1799983 and RAAS polymorphisms rs699; rs1799752 and rs5186, and quantification of ACE activity (Fluorimetric Assay) and nitrite concentration (Chemiluminescence Method). <b>Results and Conclusion:</b>Good TS level appears to exert greater influence on SBP for G2 and G3 (G1: 125.79 ± 14.03/ G2: 119.91 ± 11.72^/G3: 119.71 ± 10.85) and on NO₂ for G3 (G1: 0.42 ± 0.25/ G2: 0.54 ± 0.45/ G3: 0.71 ± 0.52). No associations were observed between eNOS and RAAS polymorphisms, but the epistasis was identified between eNOS polymorphism, rs2070744, and RAAS polymorphism, rs699, revealing a statistically significant interaction (<i>p</i> = .0235) with training score of 0.63, a training test accuracy of 0.61 and a cross-validation consistency of 10/10. This result suggests an increased risk of hypertension.

**引言：** 血压（blood pressure, BP）的变异部分由遗传因素决定，肾素-血管紧张素-醛固酮系统（renin-angiotensin-aldosterone system, RAAS）与内皮型一氧化氮合酶（endothelial nitric oxide synthase, eNOS）的部分多态性与高血压（hypertension, HT）存在关联。反之，体育运动被视作高血压控制、治疗及预防的非药物干预手段。
**研究目的：** 本研究旨在探讨eNOS与RAAS多态性、二者的上位互作效应，以及相关体液因子在正常血压、高血压前期及老年高血压受试者血压调控中的作用，并分析运动状态（training status, TS）水平对该关联的调节效应。
**研究方法：** 本研究共纳入155名老年受试者（年龄为66.94±6.83岁），完成以下检测项目：采用AAHPERD综合体能测试评估总体功能健康指数（general functional fitness index, GFFI）；测量收缩压与舒张压（systolic and diastolic blood pressure, SBP and DBP）；采集血液样本用于DNA提取；分析eNOS基因多态性位点rs2070744、rs61722009及rs1799983，以及RAAS基因多态性位点rs699、rs1799752及rs5186；并采用荧光测定法（Fluorimetric Assay）定量检测血管紧张素转换酶（angiotensin-converting enzyme, ACE）活性，以化学发光法（Chemiluminescence Method）测定亚硝酸盐（NO₂）浓度。
**结果与结论：** 结果显示，良好的运动状态（TS）水平对G2与G3组受试者的收缩压（SBP）具有更显著的调控作用（G1组：125.79±14.03；G2组：119.91±11.72；G3组：119.71±10.85），且对G3组的亚硝酸盐（NO₂）水平亦存在显著影响（G1组：0.42±0.25；G2组：0.54±0.45；G3组：0.71±0.52）。本研究未观察到eNOS与RAAS多态性之间存在关联，但成功鉴定出eNOS多态性位点rs2070744与RAAS多态性位点rs699之间存在上位互作效应，二者呈现具有统计学意义的互作关联（p=0.0235），对应的训练得分为0.63，训练测试准确率为0.61，交叉验证一致性为10/10。该结果提示受试者罹患高血压的风险升高。