The G Allele of the rs12050217 Polymorphism in the BDKRB1 Gene Is Associated with Protection for Diabetic Retinopathy.

ABSTRACT

Purpose: The plasma kallikrein-kinin system is activated during vascular injury caused by diabetic retinopathy (DR), being involved in hyperpermeability and inflammation. Bradykinin B1 receptor (B1R) is expressed in human retina, and its levels are increased in murine models of diabetes. Experimental studies reveal that B1R antagonists ameliorate retinal injury caused by diabetes in rodents. Thus, the aim of this study was to investigate the association between the rs12050217A/G polymorphism in the BDKRB1 gene, the gene that codifies B1R, and DR in type 2 diabetes mellitus (T2DM) patients. Methods: We analyzed 636 T2DM patients and 443 non-diabetic subjects. T2DM patients were categorized by the presence of non-proliferative DR (NPDR, n = 267), proliferative DR (PDR, n = 197), and absence of DR (n = 172). 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 non-diabetic subjects (P > 0.05). The presence of the genotypes containing the rs12050217 G allele was less frequent in patients with PDR when compared to patients with NPDR and without DR (32.0%, 41.9%, and 43.0%, P = 0.045, respectively). Interestingly, the presence of G allele was associated with ~40% protection for PDR, which was confirmed after correction for the presence of hypertension, ethnicity, age, HDL, and gender (odds ratio = 0.616, 95% confidence interval 0.385-0.986, P = 0.043). Conclusion: For the first time, we showed that BDKRB1 rs12050217 G allele is associated with protection for the advanced stage of DR in T2DM patients; however, further studies are needed to confirm this finding.