Association of TIMP2 Gene Variants With Development of Diabetic Retinopathy

Background/Aim: Diabetic retinopathy (DR) is a common comorbidity of diabetes involving the formation of abnormal vascular structures in the retina. Tissue inhibitor of metalloproteinases 2 (TIMP2), initially identified as a key mediator of extracellular matrix turnover, is pivotal for inflammatory processes and tissue homeostasis. The current study examined the influence of TIMP2 gene variations on the risk for DR. Materials and Methods: We investigated the association of TIMP2 gene variations with DR by analyzing four single-nucleotide polymorphisms (SNPs) of the TIMP2 gene (rs16971783, rs2889529, rs7220980, and rs8068674) in a cohort of 672 patients with DR and 919 diabetic controls with normal ophthalmoscopic findings. Results: Our results showed that rs16971783 of TIMP2 gene was associated with a higher risk for DR (TA vs. TT, AOR=1.445, p=0.028; TA+AA vs. TT, AOR=1.179, p=0.046). We further demonstrated that the association of rs16971783 with DR was exclusively observed in diabetic individuals with proliferative DR (TA vs. TT, AOR=1.827, p=0.035; TA+AA vs. TT, AOR=1.351, p=0.027), whereas not detected among those who suffered from non-proliferative DR. In addition, preliminary exploration of gene expression data from public resources revealed that rs16971783 regulated TIMP2 gene expression in various human tissues. Conclusion: Allele-specific expression of TIMP2 gene might contribute to the progression of DR.