AGTR1基因甲基化及其与超重、腹型肥胖联合作用对糖尿病患病影响

AGTR1 gene methylation and its joint action with overweight and abdominal obesity on diabetes mellitus

目的了解AGTR1基因甲基化及其与超重、腹型肥胖联合作用对糖尿病患病的影响,为糖尿病的防治提供科学依据。方法于2015年4—9月采用分层随机抽样方法在福建省福清市、长乐市和南安市抽取60个社区共8 371名常住居民进行问卷调查和体格检查;采用高分辨率熔解曲线(HRM)方法抽取其中在福清市3个社区按性别、年龄、文化程度、婚姻状况进行1:4病例对照匹配的205名居民进行AGTR1基因甲基化水平测定,并采用叉生分析表结合logistic回归模型与Delta法分析AGTR1基因甲基化与超重、腹型肥胖联合作用对糖尿病患病的影响。结果福建省福清市、长乐市和南安市8 371名居民中,患糖尿病者705例,糖尿病患病率为8.42%;经性别、年龄、文化程度、婚姻状况、吸烟情况、饮酒情况、参加体育锻炼情况、规律饮食情况等混杂因素调整后,多因素非条件logistic回归分析结果显示,超重者患糖尿病的风险为正常体重者的1.999倍(OR=1.999,95%CI=1.671~2.392),腹型肥胖者患糖尿病的风险为非腹型肥胖者的1.272倍(OR=1.272,95%CI=1.060~1.527);经吸烟情况、饮酒情况、参加体育锻炼情况、规律饮食情况、体质指数(BMI)、腰臀比(WHR)等混杂因素调整后,多因素条件logistic回归分析结果显示,AGTR1基因低甲基化者患糖尿病的风险为高甲基化者的2.222倍(OR=2.222,95%CI=1.093~4.518);联合作用分析结果显示,超重且AGTR1基因低甲基化者患糖尿病的风险为非超重且AGTR1基因非低甲基化者的3.584倍(OR=3.584,95%CI=1.175~10.928),腹型肥胖且AGTR1基因低甲基化者患糖尿病的风险为非腹型肥胖且AGTR1基因非低甲基化者的4.141倍(OR=4.141,95%CI=1.138~15.075);交互作用分析结果显示,超重和腹型肥胖与AGTR1基因低甲基化均不存在相乘和相加交互作用(均P> 0.05)。结论 AGTR1基因低甲基化水平与超重、腹型肥胖联合作用均可增加糖尿病的患病风险。

Objective To investigate angiotensin Ⅱ type Ⅰreceptor（AGTR1） gene methylation and its effect combined with overweight, abdominal obesity on diabetes, and to provide a basis for prevention and treatment of diabetes. Methods Using stratified random sampling, we conducted a questionnaire survey and physical examination among 8 371 permanent residents aged ≥ 18 years in 60 communities in Fuqing, Changle, and Nan＇an municipality of Fujian province from April to September2015. We also carried out a 1 ： 4 gender-, age-, education-, and marital status-matched case-control study to determine the methylation level of AGTR1 gene with high-resolution melting（HRM） analysis among 205 residents in 3 communities of Fuqing municipality. The joint effect of AGTR1 methylation with overweight and abdominal obesity on the prevalence of diabetes was analyzed with cross-sectional analysis, logistic regression analysis, and Delta method. Results Among the 8371 participants, 705 were identified with diabetes and the prevalence of diabetes was 8.42%. The results of multivariate nonconditional logistic regression analysis revealed that the participants with overweight or with abdominal obesity had a 1.999-fold（odds ratio [OR] = 1.999, 95% confidence interval [95% CI]： 1.671-2.392） or a 1.272-fold（OR = 1.272, 95% CI： 1.060-1.527） risk of developing diabetes after adjusting for potential confounding factors as gender, age, education, marital status,smoking, alcohol consumption, participation in physical exercise, and regular diet; the results also demonstrated that in comparison to those with hypermethylation of AGTR1 gene, the participants with the low methylation were more likely to have diabetes（OR = 2.222, 95% CI： 1.093-4.518） after adjusting for smoking, alcohol consumption, participation in physical exercise, regular diet, body mass index（BMI）, and waist-to-hip ratio（WHR）. Further analyses on joint effect disclosed that the participants with both overweight and low AGTR1 hypomethylation had a 3.584-fold（OR = 3.584,95% CI：1.175-10.928） risk of developing diabetes compared to those with neither overweight nor low AGTR1 hypomethylation and that the participants with both abdominal obesity and low AGTR1 hypomethylation had a 4.141-fold（OR = 4.141,95% CI：1.138-15.075） risk of developing diabetes in contrast to those with neither abdominal obesity nor low AGTR1 hypomethylation. There were no multiplication and additive interaction between overweight or abdominal obesityand low AGTR1 hypomethylation based on interaction analysis（all P〉0.05）. Conclusion Low AGTR1 gene hypomethylation level combined with overweight or abdominal obesity can increase the risk of diabetes among community adults.