NEDD4L基因与四川藏族高血压氢氯噻嗪疗效的关联分析  

The association study of NEDD4L gene SNPs with hydrochlorothiazide treatment in Sichuan Tibetan patients with hypertension

作　　者：孟庆滔 钱稚平 王斯[1] 刘凯[1] 何霁云[1] 何森[1] 张昕[1] 王勇[1] 陈晓平[1] 

机构地区：[1]四川大学华西医院心内科,成都610041 [2]甘孜藏族自治州人民医院心内科

出　　处：《临床心血管病杂志》2017年第4期331-336,共6页Journal of Clinical Cardiology

基　　金：四川省科技厅支撑计划项目(No:2012SZ0131)

摘　　要：目的:研究四川藏族轻度高血压患者对小剂量氢氯噻嗪治疗的反应和耐受性,并比较神经前体细胞表达发育调控样蛋白4(NEDD4L)基因SNP位点与降压反应的关联。方法:对符合纳入排除标准的120例初发藏族轻度高血压患者,进行问卷调查、体格检查、血清学检测;提取其外周血白细胞DNA进行PCR扩增,使用分子质谱法对NEDD4L基因3个SNP位点rs2288774、rs3865418和rs4149601进行分型。并对所有入选患者进行为期1个月的小剂量氢氯噻嗪(12.5mg,qd)干预。结果:该群体用药前的平均收缩压为153.73mmHg(1mmHg=0.133kPa),用药后的平均收缩压为143.52 mmHg,显著下降10.21 mmHg;用药前的平均舒张压为90.94mmHg,用药后的平均舒张压为85.16mmHg,显著下降5.78mmHg。40例血压达标,达标率为36.70%。协方差分析未发现上述位点不同基因型携带者的血压下降值有显著差异。多元线性回归也未发现上述位点与血压下降值有显著关联。结论:小剂量氢氯噻嗪可在短期内显著降低藏族轻度高血压患者的血压;但未发现以上SNP位点对降压有显著影响。Objective：To investigate the reaction and tolerance of small dose hydrochlorothiazide （HCTZ） ther- apy in Tibetan patients with mild hypertension. And to compare the antihypertensive effects of hydrochlorothiazide （HCTZ） in patients with different genotypes of neuronal precursor cell expressed developmentally down regulated 4-like （NEDD4L） gene. Method： The 120 Tibetan patients with mild hypertension were surveyed and examined by questionnaire investigations, physical examinations, as well as serological tests. Moreover, their DNA were extracted from the peripheral white blood cells and amplified by the Polymerase Chain Reaction （PCR）. Then, the 3 SNP genotyping （rs2288774, rs3865418 and rs4149601） belonging to the NEDD4L genes were identified using the Molecular Mass Spectrometry. Small dose hydrochlorothiazide （12.5 mg qd） treatment was given to them for one month. Result：After treatment, systolic blood pressure of the patients decreased significantly from 153.73 mmHg to 143. 52 mmHg, and diastolic blood pressure reduced significantly from 90. 94 mmHg to 85.16 mmHg. The 40 patients got blood pressure ≤140/90 mmHg after HCTZ therapy, and the rate of BP control was 36.70%. Analysis of covariance showed no differences in BP reduction among the carriers of distinct genotypes. Multiple regression analysis found no significant relationship between the BP reduction and SNP genotyping mutation. Conclusion： In a relatively short period, small dose hydrochlorothiazide therapy could effectively reduce the blood pressure in Tibetan patients with mild hypertensive. However, no significant differences were discovered among the patients carried distinct SNP genotyping.

关 键 词：神经前体细胞表达发育调控蛋白4 藏族 原发性高血压 氢氯噻嗪 

分 类 号：R544.1[医药卫生—心血管疾病]