血管紧张素Ⅱ受体基因多态性与醛固酮腺瘤发病风险的相关性

Association of Polymorphisms in Angiotensin Ⅱ receptor genes with aldosterone-producing adenoma

目的探讨血管紧张素Ⅱ 1型受体及2型受体基因(AT1R、AT2R)多态性与中国汉族人群肾上腺醛固酮腺瘤(A-PA)发病风险的相关性。方法提取148例APA组织DNA及192例正常人群外周血DNA;采用MGB-Taqman探针法对AT1R基因(rs5182、rs5186)和AT2R基因(rs5194、rs1403543)4个SNP位点进行基因型检测。SNPassoc 1.5-3软件分析Hardy-Weinberg平衡以及AT1R、AT2R基因多态性与APA发病危险的关联性。结果 4个位点基因型分布均符合Hardy-Weinberg平衡(P均>0.05)。APA组AT2R基因rs5194位点A等位基因频率(0.49)要高于正常人群组(0.35)(χ2=12.08,P=0.001)。以rs5194纯合子基因型GG为参照,纯合子基因型AA和杂合子基因型GA的APA发病风险均增高(OR=2.66,95%CI=1.45-4.87和OR=1.67,95%CI=1.02-2.74)。rs5194位点多态性在显性模型、隐性模型以及加性模型中均与APA发病相关联(OR=1.94,95%CI=1.23-3.06,P=0.003;OR=2.01,95%CI=1.17-3.45,P=0.01;OR=1.64,95%CI=1.21-2.20,P=0.001)。结论AT2R基因rs5194位点多态性和APA发病相关联,对该SNP位点的检测可能可以对预测APA的发病危险提供有用的遗传信息。

Objective To obtain genetic data of some commom genetic variants within angiotensin II receptor genes （AT1R, AT2 R） locus from aldosterone-producing adenoma （APA） patients and normal people in Chinese Han population. We analyzed the association between polymorphisms in AT1R and AT2 R genes and the risk of APA. Methods Genomic DNA was extracted from adenoma tissues of 148 APA patients and peripheral blood of 192 subjects as controls. MGB-Taqman probe was used to detect genotype of 4 SNP loci （rs5182, rs5186, rs5194 and rs1403543） within AT1R and AT2R genes. Hardy-Weinberg equilibrium （HWE） and genotype frequencies between cases and controls of each polymorphism locus were determined by SNPassoc in R statistics program 2.7.0 software package. Results The sex, age and BMI of APA patients and subjects have no significant difference （P〉0.05）. Four SNP loci were successfully detected. The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium （HWE） in APA and control group （P〉0.05）. Of the 4 loci, rs5194 SNP at AT2R gene was most significantly associated with APA in additive （OR=1.64, 95%CI=1.21-2.20, P=0.001）, dominant （OR=1.94, 95%CI=1.23-3.06, P=0. 003）, and recessive model （OR=2.01, 95%CI=1.17-3.45, P=-0.01）. The allele A frequency at rs5194 was significantly higher in APA group （0.49） than that in normal controls group （0.35） （X2=12.08, P=0.001）. Homozygotic genotype AA and heterozygotie genotype GA had an increased risk of APA compared to GG genotype （OR=2.66, 95% CI=1.45-4.87; OR=1.67, 95% CI=1.02-2.74）. Conclusion Rs5194 SNP at AT2R gene was associated with the risk of APA.