上海某区人群AT1R和AGT基因多态与肾功能指标的相关性

Association of Genetic Polymorphisms of Angiotensin II Type I Receptor and Angiotensinogen with Kidney Function in Adults of a District of Shanghai

[目的]探讨血管紧张素Ⅱ1型受体（angiotensin Ⅱ type Ⅰ receptor,AT1R）、血管紧张素原（angiotensinogen,AGT）基因多态性与肾功能等临床指标的关系。[方法]多阶段随机抽取2 026例上海市浦东新区20-80岁的社区居民为研究对象,排除服用降压药、降脂药和有亲缘关系者。收集人口学资料和生活方式等信息;测量身高、体重;检测血肌酐、尿肌酐及尿微量白蛋白等指标;计算尿白蛋白/肌酐比值（albumin-to-creatinine ratio,ACR）和肾小球滤过率（estimated glomerular filtration rate,eGFR）;应用聚合酶链-高温连接酶连接检测技术（PCR-LDR）检测基因多态性。[结果]2 026例成年人群中,AT1R A1166C和AGT rs699不同基因型在性别构成、年龄均值及吸烟和饮酒的比例上差异均无统计学意义（P〉0.05）。所有研究对象按性别分层,上述位点尿肌酐、尿白蛋白、血肌酐、ACR、eGFR均值,及白蛋白尿和肾功能下降的比例两类基因型间差异均无统计学意义（P〉0.05）;按年龄分层,45岁及以上人群AT1R A1166C AA基因型的eGFR均值低于AC/CC基因型,差异有统计学意义（P〈0.05）。logistic回归分析结果未发现基因型与白蛋白尿或肾功能下降有关联。广义线性模型分析结果也未发现两种突变等位基因携带之间的交互效应（P〉0.05）;以eGFR为应变量时,AT1R A1166C C等位基因携带与年龄组间交互项有统计学意义（P=0.039）,进一步按年龄组分层,AA与AC/CC之间差异无统计学意义（P〉0.05）。[结论]对于所有对象,未发现AT1R A1166C和AGT rs699多态性与肾功能指标的统计学关联,而中老年人群AT1R A1166C C等位基因突变与eGFR增高有统计上的关联。

[Objective] To evaluate the association between the genetic polylmorphisms of angiotensin Ⅱ type Ⅰ receptor（AT1R）, angiotensinogen（AGT） and kidney function in adult residents of Pudong New Area of Shanghai. [Methods] Residents aged 20-80 years（n=2 026） were randomly selected from Pudong New Area of Shanghai through multistage sampling, excluding those who had ever taken antihypertensive, anti-glycemic, or antilipemic medications, as well as being relatives. Information on demographic characteristics and lifestyle and measurements of height and weight were collected. Plasma levels of creatinine and urinary levels of albumin and creatinine were tested. Urinary albumin-to-creatinine ratio（ACR） and estimated glomerular filtration rate（eGFR） were calculated to evaluate renal function. Single nucleotide polymorphisms at AT1 R A1166C and AGT rs699 were genotyped by polymerase chain reaction-ligase detection reaction（PCR-LDR） method. [Results] No significant association was observed for genotypes at AT1 R A1166C or AGT rs699 with mean age, gender, drinking, or smoking（P 〉0.05）. For all or any age-stratified participants, no significant association was observed for genotypes at AT1 R A1166C or AGT rs699 with any kidney function index such as urinary creatinine, albumin, creatinine, ACR, or eGFR（P 〉0.05）. In individuals more than 45 years old, the average level of eGFR for AA was lower than that for AC/CC at AT1 R A1166C（P 〈0.05）. The prevalence of albumin or decreased kidney function did not differ by genotypes at AT1 R A1166C or AGT rs699 in logistic regression analysis（P 〉0.05）. The results of generalized linear model analysis showed no interaction between AT1 R A1166C and AGT rs699 in relation to the measured phenotypes（P 〉0.05）. While eGFR was defined as a dependent variable, interaction was found between genotypes at AT1 R A1166C and age groups（P=0.039）, but eGFR did not differ for genotypes in each age group（P 0.05）. [Conclusion] For all the subjects, AT1 R A1166C or AGT rs699 genetic polylmorphism is not associated with kidney function, while C mutation at AT1 R A1166C associates with higher eGFR in middle-aged and elderly populations.