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目的:研究醛固酮合酶基因(CYP11B2)和11-β羟化酶基因(CYP11B1)多态性与醛固酮瘤(Aldosterone-producing adenoma,APA)术后持续性高血压的相关性。方法:对电话随访到的2002～2007年在同济医院就诊的93例APA患者采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性(野生型/转位型),分析上述位点与预后(血压恢复好/坏)的关系。结果:rs4539与术后高血压相关(P=0.008),校正性别、年龄、身体质量指数后仍相关(P=0.002)。单体型分析表明,整体上CYP11B2-CYP11B1单体型与术后持续性高血压相关(Global sim,P=0.035)。多元回归模型表明,除了传统的风险因素包括术前较长的高血压持续时间、高血压家族史外,单体型H2[OR 1.363(95%CI 1.094～1.689)]、H3[OR 1.555(95%CI 1.148～2.107)]是术后持续性高血压的风险因素,且术前收缩压与单体型H2、H3对术后高血压有协同促进作用(均P<0.005)。结论:APA患者术后血压恢复受到CYP11B2/B1多态性的影响,术前尽早控制血压有助于术后血压的恢复。
Objective: To investigate the relationship between the polymorphisms of aldosterone synthase gene (CYP11B2) and 11-β hydroxylase gene (CYP11B1) and persistent hypertension after aldosterone-producing adenoma (APA). Methods: DNA polymorphisms including rs1799998, rs4539 and rs6439 of CYP11B2 gene and rs6410 and rs6387 of CYP11B1 gene were detected by Taqman probe in 93 patients with APA who visited Tongji Hospital from 2002 to 2007. Two pairs of independent PCR was used to detect the CYP11B2 gene intron2 polymorphism (wild type / translocation) and the relationship between the above sites and prognosis (good / bad blood pressure recovery) was analyzed. Results: rs4539 was associated with postoperative hypertension (P = 0.008). Correlation of sex, age and body mass index was still significant (P = 0.002). Haplotype analysis revealed overall CYP11B2-CYP11B1 haplotype was associated with postoperative persistent hypertension (Global sim, P = 0.035). Multivariate regression models revealed that haplotype H2 [OR 1.363 (95% CI 1.094 ~ 1.689]], H3 [OR 1.555 (95) % CI 1.148 ~ 2.107)] were the risk factors of postoperative persistent hypertension. Systolic blood pressure (systolic blood pressure) and preoperative systolic blood pressure (systolic blood pressure) were associated with postoperative hypertension with haplotypes H2 and H3 (all P <0.005). Conclusion: The postoperative BP recovery in APA patients is affected by the CYP11B2 / B1 polymorphism. Preoperative control of blood pressure as soon as possible is helpful for postoperative BP recovery.