血管紧张素转换酶醛固酮合酶α-内收蛋白基因多态性与肾损害的关系

Relationship of gene polymorphisms of angiotensin convertion enzyme, aldosterone synthase and α- adducin with subclinical renal lesion.

目的研究血管紧张素转换酶（ACE）基因I／D、醛固酮合酶（CYP11B2）基因-344T／C和α-内收蛋白（α—adducin）基因460G／T多态性与肾损害的关系。方法应用聚合酶链式反应（PCR）和限制性片段长度多态性（RFLP）技术检测604例血压正常者及1080例血肌酐（Cr）〈2mg／L高血压患者的ACE、CYP11B2、α-adducin基因多态性。用Cockcroft—Gauh（CG）公式计算的内牛肌酐清除牢（Ccr）评价肾功能，分别将血压正常和高血压组分为肾功能正常组（Ccr≥60ml／min）及肾损害组（Ccr〈60ml／min）。结果经方差分析、列联χ^2和χ^2分割检验表明，ACE、CYP11B2和基因各自的基因型分布符合Hardy－Weinberg遗传平衡。血压肾功能正常、血压正常肾损害、离血压肾功能正常与高血压肾损古4组比较：血压正常肾损害损和高血压肾损害组年龄大于血压肾功能正常组和高血压肾功能正常组，分别为（72．7±11．4）岁、（70．5±10．1）岁与（57．4±11．1）岁和（58．0±10．1）岁（均为P〈0．01），而血压正常肾损害组和高血压肾损害组、血压肾功能正常组与高血压肾功能正常组间比较，芳肆尤统计学意义（P〉0．05）。ACE—DD基因型分布频率在高血压肾损害组最高为22．6％（57／252），α－adducin TT基闪型分布频率在血压肾功能正常组最低为13．3％（68／512），分别与其他3组比较，差件有统计学意义（均为P〈0．01），其他3组基因型分布频率比较，差异无统计学意义（均为P〉0．05）。CYP11B2各基因型的分布印频率4组比较，差异无统计学意义（均为P〉0．05）。结论随增龄．肾功能芹常增加．ACE-DD基因型与高血压肾损害相关，α—adducin—TT基因型与高血压和肾损害均相关，但未发现CYP11B2基闪多态件与肾损害的关系。

Objective To investigate the relationship of gene polymorphisms of angiotensin convertion enzyme （ACE）, aldosterone synthase （CYP11B2）and a adducin with subclinical renal lesion. Methods I/D polymorphism of ACE gene, 344T/C polymorphism of CYP11B2 gene and 460G/T polymorphism of α-adducin gene were detected by polymerase chain reaction （PCR） and restrictive fragment length polymorphism（RFLP） in 604 normotensive subjects and 1081 primary hypertensive patients whose creatinine （Cr） were less than 2mg/L. The primary hypertensive and normotensive subjects were divided respectively into normal group （Ccr≥60ml/min） and subclinical renal lesion （Ccr≥60 ml/min） group, according to creatinine clearance rate （Ccr） calculated by Cockcroft-Gault equation. Results ANOVA, contingency χ^2 and partition of chi square were selected. The frequencies of different genotypes of ACE, CYP11B2, and α-adducin were in agreement with Hardy-Weinberg equilibrium in our study. Normal renal function group （A group, n=512） and subclinical renal lesion group （B group, n=92） in normotensive subjects, and normal renal function group （C group, n 828） and subclinical renal lesion group （D group, n= 252） in hypertensive patients were compared. The patients in B and D groups were older than those in A and C groups （P〈0. 01）. But there were no significant differences in the age between B and D groups, and between A and C groups. The frequency of ACE-DD genotype in D group was the highest （22.6%） among four groups and the frequency of a adducin-TT genotype in A group was the lowest （13.3%） among four groups （all P〈0.01）. The differences of genotype frequencies of ACE and α-adducin genes among other three groups were not significant. No significant difference was found in frequencies of genotypes of CYP11B2 among four groups. Conclusions Subclinical renal lesion is increased with the aging. ACE-DD genotype is related with hypertension and subclinical renal lesion, while α- adducin-TT genotype is related with hypertension and subclinical renal lesion. Association between the genotypes of CYP11B2 and subclinical renal lesion is not found.