Role of TCF7L2 and PPARG2 Gene Polymorphisms in Renal and Cardiovascular Complications among Patients with Type 2 Diabetes: A Cohort Study

Abstract

Background: The emerging renal and cardiovascular complications of type 2 diabetes (T2DM) genetics involves differently assembled gene variants including transcription factor 7-like 2 (TCF7L2) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) polymorphisms. However, the relevance of these genes for complication prediction has not been extensively tested. Methods: We analyzed the SNP rs7903146 variants in TCF7L2 and PPARG2 gene polymorphisms for their contribution to the incidence of chronic kidney disease (CKD) and cardiovascular complications in a prospective cohort study. All T2DM patients were followed up to estimate the glomerular filtration rate and cardiovascular outcomes. Cox proportional hazards regression models were used to estimate the genotype effect on the incidence of CKD and vascular complications. Results: A total of 422 patients were included. SNP rs7903146 variants in the TCF7L2 gene were classified into 3 groups: CC, 385 patients (91.2%), CT, 32 patients (7.6%), and TT, 5 patients (1.2%), while in the PPARG2 gene they were classified into 2 groups: Pro12Pro, 404 patients (95.7%) and Pro12Ala, 18 patients (4.3%). The prevalence of CKD, cardiovascular disease, and death at the end of the 5-year follow-up was 16.8, 29, and 7.9%, respectively. The Pro12Ala variant of the PPARG2 gene was significantly associated with increased CKD risk at the end of the study (adjusted HR 3.45, 95% CI 1.01–11.77, p = 0.046); it showed a significant association with increased cerebrovascular risk, but not cardiovascular disease and mortality. No genotype effect of rs7903146 in the TCF7L2 gene was apparent on renal and cardiovascular complications, except the TT variant of rs7903146 increased cardiovascular events when compared with the non-TT variant. Conclusion: The findings of our study were that the Pro12Ala variant in the PPARG2 gene was associated with risk of developing CKD and cerebrovascular disease in Asian T2DM subjects in a prospective cohort study. The TCF7L2 polymorphism was not associated with cardiovascular outcomes.