四川藏族僧尼高血压氢氯噻嗪疗效及其与α-内收蛋白基因单核苷酸多态性的关联分析

摘要

目的:研究四川省甘孜州藏族僧尼群体轻度高血压患者对小剂量氢氯噻嗪治疗的反应和耐受性,比较α-内收蛋白基因SNP位点不同基因型携带者的降压反应.方法:对符合纳入排除标准的120例藏族初发、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,采用分子质谱法对α-内收蛋白基因SNP位点rs17833172和rs4961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/d)干预.结果:该研究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143.52mmHg,较用药前血压值显著下降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,较用药前血压值显著下降5.78mmHg.药物达标总人数为40例,达标率为36.7％.协方差分析未发现上述四个位点不同基因型携带者的血压下降值具有显著差异.多元线性回归也未发现上述SNP位点的突变与血压下降值有显著关联.结论:小剂量氢氯噻嗪可以在短期内显著降低藏族轻度高血压患者的血压水平;未发现以上SNP位点对降压程度有显著影响.%Objective:To investigate the reaction and tolerance of the Tibetan initially-found mild hypertension patients to the small dose hydrochlorothiazide (HCTZ) therapy,among the monks and nons living in Tibetan Autonomous Prefecture of Garzê,Sichuan province.To compare the antihypertensive effects of ydrochlorothiazide (HCTZ) in patients with different genotypes of oα-adducin.Methods:120 initially-found mild hypertensive patients who met the inclusion and exclusion criteria 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).And then,the 2 SNP locuses (rs17833172 and rs4961) belonging to the α-adducin gene were identified using the Molecular Mass Spectrometry.Small dose hydrochlorothiazide (12.5mg qd) treatment was given to them for one month.Results:After treatment,systolic blood pressure of the patients decreased significantly by 10.21mmHg and diastolic blood pressure reduced significantly by 5.78mmHg.There are 40 patients who have blood pressure ≤ 140/90 mmHg after HCTZ therapy,and the rate of BP control was 36.70％.Analysis of covariance showed no significant BP reduction differences among the carriers of distinct genotypes.Similarly,multiple regression analysis still found no significant relationship between the BP reduction and SNP locuses' mutation.Conclusion:In a relatively short period,small dose hydrochlorothiazide therapy could effectively reduce the blood pressure of the Tibetan mild hypertensive patients.However,no significant differences were discovered among the patients carrying distinct SNP locuses.