血管紧张素Ⅱ受体基因多态性与醛固酮腺瘤患者术后血压恢复的关系

Association of polymorphisms in angiotensin Ⅱ receptor genes with postoperative hypertension risk of patients with aldosterone producing adenoma patients

目的 探讨血管紧张素Ⅱ1型受体（AT1R）和2型受体（AT2R）基因多态性与肾上腺醛固酮腺瘤（APA）患者术后血压恢复情况的相关性.方法 提取148例APA手术患者腺瘤组织DNA,采用小沟结合子（MGB）-Taqman探针法对AT1R基因rs5182、rs5186和AT2R基因rs5194、rs1403543 4个单核苷酸多态性（SNP）位点进行基因型检测；随访APA患者术后血压恢复,术后6个月血压＜ 140/90 mm Hg（1 mm Hg =0.133 kPa）且不需任何抗高血压药物者认为血压恢复正常,否则认为术后持续性高血压.SNPassoc分析Hardy-Weinberg平衡以及基因多态性与APA术后血压恢复的关系.结果 成功随访128例,术后血压恢复正常者72例,持续性高血压者56例.4个位点基因型分布均符合Hardy-Weinberg平衡（P＞0.05）,AT2R基因rs1403543 （G/A）位点多态性和术后持续性高血压相关,其纯合子GG基因型患者要比AA基因型或GA基因型患者术后出现持续性高血压的危险性高[优势比（OR）=5.00,95％可信区间（CI） =1.31～19.15,P＜0.05].结论 AT2R基因rs1403543位点多态性有助于预判APA术后血压恢复情况.

Objeetlve To study the association between polymorphisms within angiotensin ]I re- ceptor genes （ATl R, AT2R） and postoperative recovery of blood pressure （BP） in patients with aldoste- tone producing adenoma （APA）. Methods Genomic DNA was extracted from adenoma tissues of 148 APA patients. Minor groove junction （MGB） -Taqman probe was used to detect genotype of 4 single nucleo- tide polymorphism（SNP） loci （ rs5182, rs5186, rs5194 and m140354B ） within AT1R and AT2R genes. The postoperative recovery of BP in APA patients was followed up. After adrenalectomy, patients were cate- gorized as cured if they had no hypertension [ defined as systolic blood pressure （SBP） 〈 140 mm Hg （ 1 mm Hg = 0. 133 kPa） and diastolic blood pressure （DBP） 〈 90 mm Hg] and were not given any antihyper- tensive medications 6 months after surgery, or they were categorized as having persistent hypertension. Har- dy-Weinberg equilibrium （ HWE ） and genotype frequencies of each polymorphism locus were determined by SNPassoc in R statistics program 2. 7.0 software package. A P value 〈0.05 or odds ratio （OR） 1. O0 not in the range of 95% confidence interval （CI） implicated statistically significant difference. Results Total of 128 APA patients were followed up, including 72 patients with idea control of postoperative BP and 56 with persistent hypertension postoperatively. The distribution of genotypes of each locus was in accord- ance with Hardy-Weinberg Equilibrium （HWE） in the above two groups （ P 〉 0. 05 ）. Of the 4 SNPs, only rs1403543 locus in AT2R gene was associated with persistently postoperative hypertension of APA patients. APA patients with homozygotic genotype GG had an increased risk of persistently postoperative hypertension compared to patients with AA or GA genotype （OR =5.00, 95% CI= I. 31-19. 15 ,P 〈0. 05）. Conclusion Polymorphisms at rs1403543 locus in AT2R gene may be a predictor for postoperative BP recovery of APA patients.