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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 study the response and tolerability of low-dose hydrochlorothiazide in Tibetan patients with mild hypertension and to compare the association of hypotensive response with the SNP locus of NEDD4L gene in neural precursor cells. Methods: One hundred and twenty cases of newly diagnosed Mild Hypertension patients were enrolled in this study. Questionnaires, physical examinations and serological tests were performed. The peripheral blood leukocyte DNA was extracted for PCR amplification. The molecular weight of NEDD4L gene 3 SNP loci rs2288774, rs3865418 and rs4149601 for typing. All patients were enrolled in a small dose of hydrochlorothiazide (12.5 mg, qd) for one month. Results: The average systolic blood pressure before treatment was 153.73mmHg (1mmHg = 0.133kPa). The average systolic blood pressure after treatment was 143.52 mmHg, and the mean systolic blood pressure was decreased significantly by 10.21 mmHg. The average diastolic blood pressure before treatment was 90.94mmHg, Pressure was 85.16 mmHg, a significant decrease of 5.78 mmHg. 40 cases of blood pressure compliance, compliance rate was 36.70%. Covariance analysis showed no significant differences in BP lowering among carriers with different genotypes. Multivariate linear regression also did not find a significant association between these sites and BP depression. Conclusions: Low-dose hydrochlorothiazide significantly reduces blood pressure in Tibetan patients with mild Hypertension in a short period of time. However, no significant effect of these SNP sites on Hypotension was found.