Vascular Endothelial Growth Factor Gene Polymorphisms in Type 2 Diabetes Mellitus; Insertion/Deletion at -2549 is Associated with Retinopathy but not + 405 G/C Polymorphism

Background: Retinopathy is a serious ocular complication of diabetes. Vascular endothelial growth factor (VEGF) is massively unregulated in diabetic retinopathy. The objective of this study was to investigate the G + 405 C polymorphism in the 5′-untranslated region and the I/D polymorphism at the – 2549 position of the promoter region of the VEGF gene in patients with type 2 diabetes mellitus.

Methodology: In this study, 103 unrelated type 2 diabetic patients and 40 control subjects were involved in a case-control design. Genotyping of the I/D polymorphism at -2549 was analyzed by PCR and the G/C +405 polymorphism by PCR-RFLP.

Results: For +405 G/C polymorphism, there is no statistical significant difference in genotype distribution and allele frequencies in both diabetes groups when compared to control group or to each other. While I/D polymorphism at -2549 shows significant increase in ID genotype distribution in diabetes without and with retinopathy groups versus control group [OR (CI) =3.67 (1.27-10.8) & 5.5 (1.98-15.73) and P =0.01 & <0.001, respectively]. I allele is significantly increased in diabetes without and with retinopathy groups versus control group [OR (CI) = 3.99 (1.8-8.97) & 3.98 (1.84-8.71), respectively and P <0.001 for both]. There is no significant difference in genotype and allele frequencies in both diabetes groups when compared to each other (P =0.59 & 0.99, respectively).

Conclusions: Heterozygous form of I/D polymorphism and I allele at -2549 of VEGF gene might possibly be associated with a higher susceptibility to retinopathy as a complication of type 2 diabetes mellitus. While, no association was found with VEGF +405 G/C gene polymorphism.