老年原发性高血压患者AT_1-R基因A1166C多态性及降压药物对其的影响

The A1166C polymorphism of the Angiotensin Ⅱ type Ⅰ receptor gene and the response to antihypertensive agents in the elderly

目的 观察老年原发性高血压患者血管紧张素Ⅱ 1型受体 (AT1-R)基因A116 6C多态性的分布及不同基因型高血压患者对AT1受体拮抗剂 (AT1RB)和血管紧张素转换酶抑制剂 (ACEI)降压治疗的反应。方法 PCR RFLP法检测上海地区 186例老年高血压患者AT1 R基因 3’非编码区的A116 6C变异 ,测定 116 6C等位基因频率。选取 6 0例高血压患者按基因型分成AA和AC两组 ,随机进入AT1RB和ACEI治疗组 ,共 5 7例完成 2 4周随访 (AA =41;AC =16 ) ,比较治疗前后 2 4小时动态血压监测结果。结果 (1) 116 6C等位基因频率为 0 0 6 2 ;(2 )AT1RB组AA基因型高血压患者总体、白天、夜间的SBP和DBP均较治疗前下降 7 36 %、7 6 3%、6 81%和 6 4 8%、6 4 5 %、7 4 3%;AC基因型高血压患者总体的SBP及白天的SBP、DBP均较治疗前下降 5 2 0 %和 5 6 2 %、5 5 9%。ACEI组AA和AC基因型高血压患者总体和白天SBP的下降幅度分别为 6 18%、7 13%和 4 99%、5 75 %,经配对t检验均P <0 0 5。不同药物不同基因型患者降压幅度经 2× 2方差分析均P >0 0 5。结论 (1)国内老年高血压人群 116 6C等位基因的分布频率较低 ;(2 )AT1RB和ACEI对不同AT1 R基因型老年高血压患者均有降压效应 ,其疗效与是否携带 116 6C等位基因无关。

Objective To investigate the distribution of A1166C polymorphism of the type Ⅰ angiotensin Ⅱ receptor (AT 1-R) gene in elderly hypertensive population and impact of polymorphism on the responese of BP after treatment with losartan and ACEI. Methods One hundred eighty six hypertensive subjects were randomly recruited from geriatric department in Shanghai. A→C polymorphic site at 1166 nucleotide position in the 3'-untranslated region of AT 1-R is determined using restriction length polymorphism analysis of DNA generated by polymerase chain reaction(PCR-RFLP). Sixty hypertensive subjects with average age of 71±6 yrs are divided into 2 groups according to genotypes and randomized to either an losartan or ACEI. Fifty-seven patients (AA=41,AC=16) were follow-up for 24 wks. Results (1)The frequency of C allele is 0.062. (2)Losartan decreased 24 hr,daytime,nighttime SBP by 7.4%,7.6%,and 6.8% and DBP by 6.5%,6.4%,7.4%,respectively in AA homoxygotes. ACEI decreased 24 h,daytime SBP by 6.2%,7.1% in AA homoxygotes. In AC hetrozygotes, after losartan treatment,the 24 hr SBP, daytime SBP, DBP were reduced by 5.2%, 5.6%, 5.6% in AC hetrozygotes. After ACEI treatment, the 24 hr SBP daytime SBP were reduced by 5.0%,5.8% in AC hetrozygotes. 2×2 fractorial analysis showed no interaction between genotypes and the effect of treatment. Conclusion A low allele frequency of A1166C was found in elderly Shanghai hypertensive. Although losartan and ACEI reduced SBP and DBP,no difference in response rate has been found in homozygotes and hetrozygotes. It seems the effect of losartan and ACEI on hypertension was independent from the genotypes of the patients with hypertension.