Abstract. Type 2 diabetes (T2D) is defined by high levels of glucose in the blood. The collagen IV level is associated with conditions of hyperglycemia and insulin resistance. Collagen type IV α3 chain (COL4A3) is a structural protein of the extracellular matrix (ECM). Matrix metallopeptidase 9 (MMP-9) is an enzyme that degrades the extracellular matrix and its activity is moderated by TIMP metallopeptidase inhibitor 1 (TIMP-1). The aim of the current study was to examine the association between genetic polymorphisms of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) in patients with T2D. This case-control study was performed on 120 Iranian patients with T2D and 120 healthy individuals. Genotypes were analyzed using the amplification refractory mutation system-polymerase chain reaction technique. The findings demonstrated significant differences between genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms as follows: COL4A3 (G/T); TT vs. GG, odds ratio (OR)= 0.235, 95% confidence interval (CI)=0.063-0.0802 (P=0.013) and T vs. G, OR=0.592, 95% CI= 0.371-0.943 (P= 0.026);

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This study indicates that in our population, the COL4A3 rs55703767 polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism was associated with an increased risk of KC.