Association between polymorphisms in genes encoding pro- and anti oxidants proteins and the susceptibility to nephropathy in French cohorts of type 1 diabetic patients: Validation of results observed in a Brazilian series.

Abstract

Evidences suggest that a genetic predisposition determines susceptibility to chronic complications of diabetes mellitus (DM), along with chronic hyperglycemia, hypertension and dyslipidemia. Since oxidative stress has been recognized as the final element of common biochemical pathways induced by hyperglycemia, the genes that encode pro-and antioxidant enzymes are candidates to confer susceptibility to complications. A study conducted in our laboratory demonstrated the association between several polymorphisms (some of them functional) in the promoter region or the 3'UTR of genes encoding enzymes of pro-oxidant systems (NOX-2 and p22phox) and antioxidants (GCLC, GPX-4, TXNRD2 and TXN) and risk for the presence of diabetic nephropathy in type 1 DM of long duration recruited patients in different diabetes services in the Southeast and Southern Brazil. This project aims to extend this study, validating the association between the presence of diabetic nephropathy and these candidates polymorphisms in three French cohort of patients with type 1 DM (SURGENE cohort [n = 340]; GENEDIAB cohort [n = 494] and GENESIS cohort [n = 501]). Replicating results of an association between a SNP and a phenotypic trait in cohorts of patients from different geographic origins, increases the participation of that SNP and can improve understanding about its biological significance.