Interactions Among Related Genes of Renin-Angiotensin System Associated With Type 2 Diabetes

OBJECTIVE: To explore the association between epistasis among related genes of the renin-angiotensin system (RAS) and type 2 diabetes. RESEARCH DESIGN AND METHODS: Gene polymorphisms were genotyped in 394 type 2 diabetic patients and 418 healthy control subjects in this case-control study. We used the multifactor dimensionality reduction method to identify gene-gene interactions. RESULTS: No single locus was associated with type 2 diabetes, except for the insert/deletion (I/D) polymorphism of the ACE gene in female subjects. In multi-locus analyses, in male subjects the model of rs2106809 (ACE2), rs220721 (Mas), rs699 (AGT), and I/D (ACE) was significant (P = 0.043). This combination was associated with a 4.00 times (95% CI 2.51–6.38; P < 0.0001) greater prevalence of type 2 diabetes. In female subjects, the model of rs2106809 (ACE2), I/D (ACE), and rs1403543 (AGTR2) was significant (P = 0.012). This three-locus combination was associated with a 2.76 times (1.91–3.97; P < 0.0001) greater prevalence of type 2 diabetes. CONCLUSIONS: Interactions among RAS-related genes were associated with type 2 diabetes in a Chinese population.