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目的：上皮钠通道在调节机体血压方面起到重要作用，其基因变异可影响血压的变化。本研究拟验证上皮钠通道基因变异与高血压、高血压人群服用氢氯噻嗪后的降压效果，及与氢氯噻嗪低血钾及高血糖不良反应的相关性。方法本研究前瞻性纳入两组高血压病例对照人群（分别为1642例及609例）检测上皮钠通道基因型。并对542例高血压患者给予2周的氢氯噻嗪单药降压治疗，测量基线血钾、血糖等生化指标。经过长期随访，共获得456例患者的随访资料，平均随访31个月，再次测量血钾、血糖等生化指标。结果 SCN N1Ars2071244的 G 等位基因在两组高血压病例对照人群中均与高血压显著相关（OR ：1.528，95％ CI ：1.138～2.051，P ＝0.005及 OR ：2.032，95％ CI ：1.292～3.194，P ＝0.002）。矫正年龄、性别等因素后在两组人群中相关性仍显著（OR ：1.429，95％ CI ：1.042～1.960，P＝0.027及 OR ：1.779，95％ CI ：1.098～2.884，P ＝0.019）。氢氯噻嗪服药两周后，携带 rs2071244G 等位基因的患者无论是收缩压还是舒张压均比携带 CC 基因型的患者具有更显著的降压效果。携带 rs2071244G 等位基因的患者收缩压下降26.7 mmHg ，携带 CC基因型的患者收缩压下降20.1 mmHg （ P ＝0.026）。携带 G 等位基因的患者舒张压下降13.2 mmHg ，携带 CC 基因型的患者舒张压下降9.8 mmHg（P＝0.014）。在高血压人群中，服用氢氯噻嗪之前及服用后随访时，SCN N1Ars2071244不同基因型之间血钾及血糖水平、血钾及血糖变化幅度均差异无统计学意义（P＞0.05）。结论上皮钠通道 SCN N1A 基因变异 rs2071244是高血压的危险因素，对氢氯噻嗪的降压效果更敏感，但与氢氯噻嗪对血钾、血糖的不良反应无关。“,”Objective The epithelial sodium channel plays an important role in blood pressure regulation. The purpose of the study was to determine whether the variant of epithelial sodium channel is a risk factor for hypertension ,whether it has an impact on the antihypertensive response to hydrochlorothiazide and associated with side effects of hydrochlorothiazide. Methods We performed two independent case-control studies for association with hypertension (n= 1 642 and n= 609) ,and a clinical trial of hydrochlorothiazide (n = 542) for association with diuretics response.Blood potassium and glucose measurements were obtained in all the hypertensive patients pretreatment and posttreatment.Mean follow up period was 31 months. Results We found that the SCN N1A rs2071244 G allele was significantly associated with hypertension after appropriate adjustment in twocase-control studies (OR :1.429 ,95% CI :1.042-1.960 ,P = 0.027 ,in the first population ;OR :1.779 , 95% CI :1.098-2.884 ,P= 0.019 ,in the second population). The blood pressure reduction in rs2071244 G carriers after hydrochlorothiazide treatment was greater than that in CC carriers ,26.7 mmHg vs.20.1 mmHg(P= 0.026) in systolic blood pressure and 13.2 mmHg vs.9.8 mmHg(P= 0.014) in diastolic blood pressure. After treatment of hydrochlorothiazide ,the follow-up study found no relationship between rs2071244 and the level of blood potassium or blood glucose ( P > 0.05 ). Conclusions Our results support that SCN N1A rs2071244 is a genetic risk factor for hypertension ,a predictor for antihypertensive response to diuretics ,but not associated with side effects of hydrochlorothiazide.