醛固酮合酶基因和11-β羟化酶基因多态性及其单体型与醛固酮瘤发病风险的关系  

Association of aldosterone synthase and ll-beta hydroxylase genes polymorphism and haplotype with susceptibility of aldosterone producing adenoma

作　　者：王保军[1] 陈路遥[1] 李新涛[1] 马鑫[1] 杨素霞[1] 欧阳金芝[2] 张旭[1] 

机构地区：[1]解放军总医院泌尿外科,北京100853 [2]解放军总医院干部诊疗科,北京100853

出　　处：《中华实验外科杂志》2014年第6期1213-1216,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81100561、81170732）

摘　　要：目的探讨醛固酮合酶基因（CYP11B2）和11-β羟化酶基因（CYP11B1）多态性及其单体型与醛固酮瘤发病风险的关系。方法提取81例醛固酮瘤患者和103例对照人群外周血DNA，应用2个独立聚合酶链反应（PCa）和TaqMan探针技术对CYP11B2和CYP11B1基因的7个多态性位点（rs6387、rs6410、rs3097、rs4539、intron2转位、rs1799998、rs13268025）进行基因分型，采用Logistic回归模型分析不同等位基因、基因型和单体型与醛固酮瘤发病风险的相关性。结果intron2转位多态性位点C等位基因在病例组中的分布频率（25．3％）高于对照组（15．0％），携带C等位基因的个体较携带W等位基因的个体发生醛固酮瘤的风险增加了1．04倍（P〈0．01）。rs13268025位点中携带C等位基因的个体较携带T等位基因的个体发生醛固酮瘤的风险增加了0．91倍（P〈0．05）。7个多态性位点间存在着不同程度的连锁不平衡。单体型分析示AGGAWTF为最常见的单体型，单体型GAGAWTF是AGGAWTF发病风险的4．43倍（P〈0．01）。结论CYP11B2和CYP11B1基因多态性与醛固酮瘤发病风险明显相关，intron2转位多态性位点的C等位基因、rs13268025位点的C等位基因、单体型GAGAWTT是醛固酮瘤发病的危险因素。Objective To evaluate the effects of aldosterone synthase （CYP11B2） and 11-beta hydroxylase （CYP11 B1 ） genes polymorphism and haplotype on the susceptibility of aldosterone producing adenoma. Methods Peripheral blood DNA was extracted from 81 aldosterone producing adenoma patients and 103 control subjects. Real-time TaqMan probes technique and two seperate PCRs were used for genotyping seven polymorphism sites of the CYPllB2 and CYPllB1 genes （rs6387, rs6410, rs3097, rs4539, intron 2 conversion, rs1799998, rs13268025）. Logistic regression model was performed to analyze the relationship of different genotypes or haplotype and the susceptibility of aldosterone producing adenoma. Resuits The frequency for allele C at site intron 2 conversion in the case group （25.3%） was higher than that in the control group （ 15.0% ）. The risk of aldosterone producing adenoma in individuals carrying C allele was increased by 1.04 times compared with the individuals carrying W allele （ P 〈 0. 01 ）. For rs13268025, the risk in individuals carrying C allele was increased by 0. 91 times （ P 〈 0. 05 ）. Linkage disequilibrium analysis showed that these seven variants were in different strengths of LD. The haplotype analysis demonstrated that AGGAWTT was the most common haplotype, and the aldosterone producing adenoma risk of GAGAWTF was 4.43 times higher than AGGAWTT （ P 〈 0. 01 ）. Conclusion There was a significant association between polymorphism in the CYP11 B2 and CYP11 B1 genes with aldosterone producing adenoma. The allele C of site intron2 conversion, the allele C of site rs13268025 and haplotype GAGAWTT might be risk factors for aldosterone producing adenoma.

关 键 词：醛固酮瘤 醛固酮合酶基因 11-β羟化酶基因 多态性 单体型 

分 类 号：R586.24[医药卫生—内分泌]