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 September 2015. 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 8 371 participants, 705 were identified with diabetes and the prevalence of diabetes was 8.42%. The results of multivariate non-conditional 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.