Bradykinin B2receptor gene polymorphism is associated with altered urinary albumin/creatinine values in diabetic patients

Abstract

Diabetic nephropathy (DN) is an important microvascular complication of both insulin-dependent and non-insulin-dependent diabetes mellitus. Considerable evidence exists that genetic predisposition is a major determinant in the development of DN. Progress in the understanding of the kinin receptor gene expression indicates their relevance in nephrology and renal pathology. In order to investigate whether clinically relevant polymorphisms of the kinin receptor genes contribute to the genetic predetermination of the renal complication of diabetes, we have initiated a retrospective study with a mixed population of 49 type 1 and 112 type 2 diabetic patients who have been followed for several years by an endocrinologist and (or) nephrologist with periodical functional tests relevant to DN (microalbuminuria, serum and urinary creatinine). The allelic frequencies of four kinin receptor polymorphisms, including three B₂R polymorphisms (the C/T^–58 promoter polymorphism, the exon 2 and exon 1 polymorphisms, all of them with assumed clinical significance) and the putative nephroprotective (G/C^–699) B₁R promoter polymorphism, were analyzed in all recruited diabetic patients. Our results indicate a significant association of the B₂R exon 1 (+/–) genotype with increased urinary albumin/creatinine values (P = 0.026) and serum creatinine levels (P = 0.028). More importantly, the (+) allele of B₂R exon 1 polymorphism was associated very significantly with lower albumin/creatinine values in these patients (P = 0.0087). Thus, the B₂R exon 1 polymorphism may represent a susceptibility marker for nephropathy progression in diabetic patients.Key words: kinin receptors, gene polymorphisms, diabetic nephropathy.