上皮细胞钠通道α亚单位（α-ENaC）基因单核苷酸多态性与四川藏族高血压氢氯噻嗪疗效的关联分析  

The association study of Alpha Subunit of the Epithelial Na＋ Channels （aENaC） gene SNPs with Hydrocholorozide treatment in Sichuan Tibetan hypertension patients

作　　者：孟庆滔 王斯[1] 刘凯[1] 何霁云[1] 何森[1] 张昕[1] 王勇[1] 石如峰 施迪 文博[1] 潘佩[1] 周雨霏[1] 朱小江[1] 廖行[1] 张鑫[1] 张强[1] 蔡亚丽[1] 刘琦[1] 严心 李欣然[1] 龚深圳 阳钰婕 陈晓平[1] 

机构地区：[1]四川大学华西医院心血管内科,四川省成都市610041

出　　处：《中国心血管病研究》2017年第6期564-569,共6页Chinese Journal of Cardiovascular Research

基　　金：四川省科技厅-支撑计划项目（项目编号：2012SZ0131）

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,并比较α-ENaC基因四个单核苷酸多态性位点（SNP）不同基因型/等位基因携带者降压反应的差异.方法 对符合纳入标准的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α-ENaC基因四个SNP位点rs2228576、rs10849447、rs13306613和rs3782727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（12.5 mg qd）干预.结果 该研究群体用药前的平均收缩压为153.73 mm Hg,用药后的平均收缩压为143.52 mm Hg,较用药前血压值下降10.21 mm Hg;用药前的平均舒张压为90.94 mm Hg,用药后的平均舒张压为85.16 mrn Hg,较用药前血压值下降5.78 mm Hg.药物达标总人数为40人,达标率为36.70％.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,但未发现以上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 Garz（e）,Sichuan province.To compare the antihypertensive effects of Hydrochlorothiazide （HCTZ） in patients with different genotypes of α-ENaC.Methods 120 initially-found mild hypertensive patients who met the inclusion and exclusion criteria were surveyed and examined by questionnaire inves-tigations,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 4 SNP locuses（rs2228576,rs10849447,rs13306613 and rs3782727） belonging to the α-ENaC genes were identified using the Molecular Mass Spectrometry.Small dose Hydrochlorothiazide （12.5 mg qd） treatment was given to them for one month.Results After treatment,systolic blood pressure of the patients decreased significantly by 10.21 mm Hg and diastolic blood pressure reduced significantly by 5.78 mm Hg.There are 40 patients who have blood pressure ≤ 140/90 mm Hg 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]ocuses 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.

关 键 词：单核苷酸多态性 僧尼 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]