Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi 221005, India.
Department of Opthamology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
J Diabetes Complications. 2017 Dec;31(12):1648-1651. doi: 10.1016/j.jdiacomp.2017.08.010. Epub 2017 Aug 26.
Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C>T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C>T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population.
This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C>T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results.
T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p<0.0001 by T allele; p=0.002 by TT and p<0.0001 by CT genotype).
The present study suggests that the functional SNP-1562C>T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis.
视网膜血管生成是糖尿病视网膜病变的一个标志。基质金属蛋白酶（MMPs）参与细胞外基质（ECM）的降解。MMP-9 基因启动子中的功能 SNP-1562C>T 导致转录活性增加。本研究旨在评估 MMP-9 基因功能 SNP-1562C>T 对北印度人群 2 型糖尿病（T2DM）患者发生增生性糖尿病视网膜病变（PDR）的风险的贡献。
这项病例对照研究共纳入了 645 名个体，其中 320 名是 T2DM 患者，其中 73 名患有 PDR，98 名患有非增生性糖尿病视网膜病变（NPDR），149 名 T2DM 患者无眼部相关疾病（DM），325 名非糖尿病健康个体作为对照组（非 DM 对照组）。采用聚合酶链反应（PCR）结合特定内切酶的限制性片段长度多态性（PCR-RFLP）分析 MMP-9 的 SNP-1562C>T 基因型。采用 DNA 测序来确定 PCR-RFLP 结果。
PDR 患者的 T 等位基因频率为 32.1%，NPDR 为 20.4%，DM 为 15.4%，对照组为 13.7%。在 PDR 患者与非 DM 对照组之间，等位基因和基因型分布均存在统计学显著差异（T 等位基因 p<0.0001；TT 基因型 p=0.002；CT 基因型 p<0.0001）。
本研究表明，MMP-9 基因启动子中的功能 SNP-1562C>T 可能是 PDR 的一个主要危险因素，因为高表达 T 等位基因可能会增加 MMP-9 的产生，从而促进视网膜血管生成。
