Arabian Gulf University, Department of Medical Biochemistry, Manama, Bahrain; Faculty of Sciences, University Tunis EL Manar, 2092 Manar II, Tunisia.
Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University Monastir, Tunisia.
J Diabetes Complications. 2022 May;36(5):108182. doi: 10.1016/j.jdiacomp.2022.108182. Epub 2022 Mar 18.
Few studies investigated the association of genetic difference in metalloproteinase-2 (MMP-2) gene with diabetic retinopathy but with mixed outcome. To investigate the association between a set of MMP-2 genetic variants and the risk of diabetic retinopathy in an Arab Tunisian population with type 2 diabetes.
A retrospective case-control study comprising a total of 779 type 2 diabetes patients with or without diabetic retinopathy was conducted. Genotyping was prepared by TaqMan® SNP genotyping qRT-PCR. The variants used were rs243865 (C/T), rs243864 (T/G), rs243866 (G/T) and rs2285053 (C/T).
The minor allele frequency (MAF) of the rs243864 MMP-2 variant was significantly higher among diabetic retinopathy patients. Setting homozygous wild type genotype carrier as reference, the rs243864T/G allele was associated with increased risk of diabetic retinopathy under the dominant, recessive, and additive models which persisted when key covariates were controlled for, while a reduced risk of diabetic retinopathy progression was seen after adjustment between non-proliferative and proliferative diabetic patients. Furthermore, the heterozygous genotype GT of the rs243866 variant is positively associated with the risk of proliferative diabetic retinopathy in the additive model. A limited linkage disequilibrium (LD) was revealed between the four-matrix metalloproteinase-2 variants. Four-loci haplotype analysis identified, GCTC, TTTC, and GCTT haplotypes to be positively associated with the risk of diabetic retinopathy.
Our findings demonstrate that the MMP-2 variant rs243864 and 243866 are related to the susceptibility to diabetic retinopathy and the progression of the disease in an Arab Tunisian population with type 2 diabetes.
很少有研究调查基质金属蛋白酶-2（MMP-2）基因的遗传差异与糖尿病视网膜病变的相关性，但结果存在差异。本研究旨在调查一组 MMP-2 遗传变异与 2 型糖尿病阿拉伯突尼斯人群糖尿病视网膜病变风险之间的关系。
这是一项回顾性病例对照研究，共纳入 779 例伴或不伴糖尿病视网膜病变的 2 型糖尿病患者。采用 TaqMan® SNP 基因分型 qRT-PCR 进行基因分型。使用的变体为 rs243865（C/T）、rs243864（T/G）、rs243866（G/T）和 rs2285053（C/T）。
rs243864 MMP-2 变体的次要等位基因频率（MAF）在糖尿病视网膜病变患者中显著升高。与纯合野生型基因型携带者相比，在显性、隐性和加性模型下，rs243864T/G 等位基因与糖尿病视网膜病变的风险增加相关，当控制关键协变量时，这种相关性仍然存在，而在非增殖性和增殖性糖尿病患者之间进行调整后，糖尿病视网膜病变进展的风险降低。此外，rs243866 变体的杂合基因型 GT 与加性模型中增殖性糖尿病视网膜病变的风险呈正相关。四个基质金属蛋白酶-2 变体之间显示出有限的连锁不平衡（LD）。四基因座单体型分析确定 GCTC、TTTC 和 GCTT 单体型与糖尿病视网膜病变的风险呈正相关。
我们的研究结果表明，MMP-2 变体 rs243864 和 243866 与阿拉伯突尼斯 2 型糖尿病患者糖尿病视网膜病变的易感性和疾病进展有关。
