Endocrine Division, Hospital de Clínicas de Porto Alegre , Porto Alegre , Rio Grande do Sul , Brazil.
Postgraduate Program in Medical Science: Endocrinology, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul , Porto Alegre , Rio Grande do Sul , Brazil.
Curr Eye Res. 2019 Sep;44(9):994-999. doi: 10.1080/02713683.2019.1610178. Epub 2019 May 15.
: 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 gene, the gene that codifies B1R, and DR in type 2 diabetes mellitus (T2DM) patients. : We analyzed 636 T2DM patients and 443 non-diabetic subjects. T2DM patients were categorized by the presence of non-proliferative DR (NPDR, = 267), proliferative DR (PDR, = 197), and absence of DR ( = 172). The rs12050217A/G polymorphism was genotyped by real-time PCR using TaqMan MGB probes. : The genotype frequencies of the rs12050217A/G polymorphism are in Hardy-Weinberg equilibrium and did not differ between T2DM patients and non-diabetic subjects ( > 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%, = 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, = 0.043). : For the first time, we showed that 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.
血浆激肽释放酶-激肽系统在糖尿病视网膜病变（DR）引起的血管损伤中被激活，参与了高通透性和炎症反应。缓激肽 B1 受体（B1R）在人视网膜中表达，其水平在糖尿病的小鼠模型中增加。实验研究表明，B1R 拮抗剂可改善糖尿病啮齿动物的视网膜损伤。因此，本研究旨在探讨 2 型糖尿病（T2DM）患者中编码 B1R 的 基因中的 rs12050217A/G 多态性与 DR 之间的关系。
我们分析了 636 名 T2DM 患者和 443 名非糖尿病对照者。根据非增殖性 DR（NPDR，n=267）、增殖性 DR（PDR，n=197）和无 DR（n=172）的存在情况，将 T2DM 患者进行分类。采用 TaqMan MGB 探针的实时 PCR 方法对 rs12050217A/G 多态性进行基因分型。
rs12050217A/G 多态性的基因型频率符合 Hardy-Weinberg 平衡，且在 T2DM 患者和非糖尿病对照者之间无差异（>0.05）。与 NPDR 患者和无 DR 患者相比，PDR 患者中含有 rs12050217G 等位基因的基因型频率较低（32.0%、41.9%和 43.0%，=0.045）。有趣的是，携带 G 等位基因的患者发生 PDR 的风险降低了约 40%，这一结果在校正高血压、种族、年龄、HDL 和性别后仍然成立（比值比=0.616，95%置信区间 0.385-0.986，=0.043）。
这是首次表明 rs12050217G 等位基因与 T2DM 患者 DR 晚期进展的保护作用相关；然而，需要进一步的研究来证实这一发现。
