Endocrine Abstracts

Background: Diabetic retinopathy (DR) is a chronic diabetic complication occurring in most diabetic patients after 20 years of disease. Progression of DR to its sight threatening stages is usually associated with worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein kinin system is activated during vascular injury, mediating important functions in inflammation, blood flow, and coagulation. Bradykinin B1 receptor (B1R) is expressed in human retina, and retinal B1R levels are increased in murine models of diabetes. Furthermore, experimental studies reveal that B1R antagonists ameliorate retinal functional abnormalities caused by diabetes in rodents. Thus, B1R gene (BDKRB1) is a candidate gene for DR.

Objective: To investigate the association between rs12050217A/G polymorphism in the BDKRB1 gene and DR in patients with type 2 diabetes mellitus (T2DM).

Methods: We analyzed 1129 T2DM patients and 416 non-diabetic subjects. T2DM patients were categorized by the presence of non-proliferative DR (NPDR, n=476), proliferative DR (PDR, n=275) and absence of DR (n=200). The local ethic committee approved the study, and all subjects signed a consent form. The BDKRB1 rs12050217A/G polymorphism was genotyped by Real-Time PCR using TaqMan MGB probes.

Results: The genotype frequencies of the BDKRB1 rs12050217A/G polymorphism are in Hardy-Weinberg equilibrium, and did not differ between T2DM patients and normoglycemic subjects (P>0.05). The presence of the minor G allele of the rs12050217 polymorphism was less frequent mainly in patients with PDR when compared to patients with NPDR and without DR (31.5, 41.8 and 41.2%, P=0.034; respectively). Interestingly, we observed that the presence of the G allele was associated with protection for PDR, which was confirmed after correction for the presence of hypertension, ethnicity, diabetes duration and age ((95% CI) =0.580 (0.398–0.843); P=0.004).

Conclusions: The BDKRB1 rs12050217 G allele is associated with protection for the advanced stage of DR in T2DM patients.