NEDD4L基因变异与氢氯噻嗪药物副作用相关性研究

Variant of NEDD4L Is Associated with Side Effect of Hydrochlorothiazide in Hypertension Patient

目的本研究拟在中国人群中验证NEDD4L基因变异rs4149601与氢氯噻嗪低血钾及高血糖副作用的关联。方法本研究共纳入456名高血压患者,留取基线临床资料并测量基线血钾、血糖等生化指标,给予氢氯噻嗪口服降压治疗,平均随访31个月,再次测量血钾、血糖等生化指标。结果携带rs4149601AA基因型与携带G等位基因的高血压人群在服用氢氯噻嗪后血钾水平及血钾的变化幅度均有显著差异(4.2mmol/l vs.4.443mmol/l,p=0.036,以及0.234mmol/l vs.0.087mmol/l,p=0.027)。携带AA基因型的高血压人群在未服用氢氯噻嗪时及服用氢氯噻嗪后血糖水平均显著高于携带G等位基因的高血压人群(6.259mmol/l vs.5.343mmol/l,p=0.001,以及6.459m mol/l vs.5.733m mol/l,p=0.032)。结论 NEDD4L基因变异rs4149601是高血压人群血糖升高的危险因素,也是高血压人群服用氢氯噻嗪后血钾减低的危险因素。

Objective The purpose of the study was to determine whether the variant of NEDD4 L rs4149601 is associated with hypopotassemia and hyperglycemia,the side effect of HCTZ.Methods A total of 456 hypertensive patients were enrolled in the HCTZ treatment.Blood potassium and glucose measurements were obtained in all the hypertensive patients pretreatment and posttreatment.Mean follow up period was 31 months.Results After HCTZ treatment,compared with carriers of the G allele,patients carrying the AA genotype had lower blood potassium（4.2mmol/l vs.4.443mmol/l,p=0.036）,greater blood potassium reductions（0.234mmol/l vs.0.087mmol/l,p=0.027）.Carriers of AA genotype had higher blood glucose than G allele carriers before and after HCTZ treatment（6.259mmol/l vs.5.343mmol/l,p=0.001;6.459mmol/l vs.5.733mmol/l,p=0.032,respectively）.Conclusions Our results support that NEDD4 L rs4149601 is a genetic risk factor for hyperglycemia in patients with hypertension,and also a risk factor for hypopotassemia in hypertensive patients treated with HCTZ.