低盐膳食下血压调节与胰岛素变化的关系及遗传机制研究

Low-sodium diet is a well-known intervention of prevention and control for hypertension and cardiovascular disease. However, some studies found that low-sodium intake will not change blood pressure substantially among some hypertensive or normotensive participants, which might be due to hyperinsulinemia. It is still unclear whether fasting insulin levels will influence the blood pressure regulation when dietary pattern transfers from general sodium intake to low-sodium intake. The research project is aimed to investigate the relationship and potential mechanism between blood pressure changes and fasting insulin changes during low-sodium diet. About 2600 non-diabetic participants, who completed a 7-day low-sodium diet intervention (NaCl intake: 3 g/d) with high sodium intake (NaCl intake: 10-19 g/d) at baseline, will be selected to measure the changes of both blood pressure and fasting insulin levels. Then we will examine the association of insulin changes with blood pressure changes during low-sodium diet intervention. Furthermore, the interaction analysis of genetic variants and insulin changes on blood pressure changes during low-sodium intervention will be conducted, which is aimed to test the genetic modification effects on the relationship between blood pressure regulation and insulin changes. For those important and targeted variants or loci identified by interaction analysis, functional studies will also be performed to explain the potential roles of those targeted variants or loci in blood pressure regulation during low-sodium diet. This project will provide both population-based and bench-based evidence of personalized dietary intervention and medication for hypertension.

低盐膳食是防控高血压和心血管疾病的重要措施。但是，部分高血压及非高血压患者减少食盐摄入后，血压降幅不大，可能与高胰岛素血症有关。由高盐膳食转入低盐膳食后，空腹胰岛素的变化是否影响低盐膳食下的血压调节，目前仍存争议。本项目以低盐膳食干预下血压变化和胰岛素变化的关系作为切入点，在2600余例非糖尿病人群中，观察由基线高盐膳食（食盐摄入10-19 克/天）转入7天低盐膳食干预（食盐摄入3 克/天）后，血压及空腹胰岛素水平的升降变化，以明确低盐膳食下血压变化是否受胰岛素变化的影响。进而，通过遗传多态位点与胰岛素变化幅度的交互作用分析，探讨遗传因素与胰岛素变化对低盐膳食下血压调节的共同影响；并通过重要位点或易感区域的功能研究探索潜在的分子机制，为个体化指导高血压膳食干预和降压治疗提供依据。

高血压是导致心血管疾病的重要危险因素之一。减少膳食盐的摄入是防控高血压和心血管疾病的重要措施。但是，既往研究提示部分高血压及非高血压患者减少食盐摄入后，血压降幅不大，可能与高胰岛素血症有关。由高盐膳食转入低盐膳食后，空腹胰岛素的变化是否影响低盐膳食下的血压调节，目前仍存争议。本项目利用前期开展的GenSalt研究，观察低盐膳食干预下血压变化和胰岛素变化的关系，并探讨相关遗传机制。. 在GenSalt研究收集的样本中，选择非糖尿病成年人1821人测定基线（食盐摄入10-19 克/天）和低盐膳食阶段（食盐摄入3 克/天）阶段的血清胰岛素水平，构建胰岛素和HOMA指数及相关表型数据库。分析表明，低盐膳食虽然能够引起收缩压、舒张压水平的显著下降，但同时也引起了胰岛素分泌增加、胰岛素抵抗水平增加，差异有统计学意义。进而在遗传关联研究中，挑选与钙离子通道阻滞剂相关的CACNA1A和CACNA1C基因的176个标签SNP位点，系统性检测发现位于CACNA1A基因的rs8182538，其少见等位基因T是血压升高的危险等位基因，具有T/T基因型的研究对象更易发生收缩压、舒张压的升高。而位于CACNA1A基因和CACNA1C基因变异可能影响由低盐膳食干预引起的胰岛素抵抗。本课题研究结果为个体化指导膳食限盐干预和高血压防控提供了新的科学依据，提示在减盐干预的同时需要监测血糖和胰岛素水平，避免胰岛素抵抗的发生。. 目前本课题资助下已经发表英文论文2篇（American Journal of Hypertension和Atherosclerosis杂志），本人为通讯作者。申请并获得教育部自然科学奖二等奖1项（本人为第6/11完成人）。