难治性高血压患者血管紧张素原、血管紧张素Ⅱ1型受体、质膜Ca2+-ATP酶1基因多态性研究

The changes of polymorphism of AGT, AGTR1, ATP2B1 gene in resistant hypertension

目的探讨血管紧张素原(AGT)、血管紧张素Ⅱ1型受体(AGTR1)、质膜Ca2+-ATP酶1(ATP2B1)基因多态性及基因-环境交互作用与难治性高血压的关联性。方法选取难治性高血压患者(RH组)59例,非难治性高血压患者(非RH组)77例,取静脉血,使用美国Axygen公司试剂盒提取全基因组DNA,应用直接测序法检测位点rs699、rs5051、rs5186及rs12817819单核苷酸多态性。结果AGT基因位点rs699、rs5051基因型频率在RH组和非RH组间的差异均有统计学意义(均P<0.05)。经logistic回归分析显示,校正性别、年龄、BMI、空腹血糖等因素后,AGT基因位点rs699基因型CC(OR=3.146,95%CI:1.163~8.510,P<0.05)、rs5051基因型TT(OR=3.146,95%CI:1.163~8.510,P<0.05)是难治性高血压的独立危险因素。AGT基因位点rs699及rs5051基因多态性与空腹血糖交互作用对难治性高血压的影响在校正性别、年龄、BMI和血脂等因素后消失。结论AGT基因位点rs699及rs5051基因多态性与难治性高血压易感性显著相关,未发现基因与环境因素的交互作用与难治性高血压相关联。

Objective To investigate the association of polymorphism of AGT,AGTR1,ATP2B1 gene and their interaction with environment with resistant hypertension(RH).Methods 59 patients with RH(RH group)and 77 hypertension patients(non-RH group)were enrolled.Genomic DNA was extracted from peripheral blood using QIAamp DNA Mini Kit(Axygen,America).Polymorphism of SNPs(rs699,rs5051,rs5186 and rs12817819)was measured using a direct sequencing method.Results The genotype frequency of rs699 and rs5051 of AGT was significantly different between RH group and non-RH group(all P<0.05).Logistic regression analysis showed that the CC genotype of rs699(OR=3.146,95%CI:1.163~8.51,P<0.05)and the TT genotype of rs5051(OR=3.146,95%CI:1.163~8.51,P<0.05)were independent risk factors of RH after adjusting age,sex,BMI,fasting glucose,blood lipid,serum creatinine,uric acid and smoking.The effects of rs699-and rs5051-fasting glucose interaction on resistant hypertension were insignificant after adjusting sex,age,BMI and blood lipid.Conclusion The polymorphism of AGT gene rs699 and rs5051,but not the interaction between rs699,rs5051 and environment,were significantly associated with resistant hypertension.