ICAM-1 K469E gene polymorphism, genotype-phenotype correlation, and retinopathy in Type 2 diabetes mellitus patients

Context: The role of genetic factors in the development of diabetic retinopathy is evident from the fact that only 50% of patients with the non-proliferative type of diabetic retinopathy progress to proliferative diabetic retinopathy. Though the K469E polymorphism of the ICAM-1 (Intercellular Adhesion Molecule-1) gene is known to increase the risk of developing Diabetic Retinopathy (DR) among Type 2 diabetic patients, its role in the development of severe DR has not been extensively studied.

Aim: Hence, we aimed to determine the risk due to association of K469E polymorphism of ICAM-1 gene and sight threatening diabetic retinopathy.

Methods: Two ml of blood collected from the patients was analyzed with PCR RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) to detect K469E (rs5498) polymorphism of the ICAM-1 gene.

Statistical analysis: Data were analyzed using IBM SPSS (Statistical Package for the Social Sciences) package, standard methods like Chi-square, T test, and multivariate logistic regression was used for comparing the variables.

Results: The frequencies of three different genotypes among the patients with STDR (Sight-threatening Diabetic Retinopathy) are 26.9% AA, 53.8% AG, and 19.3% GG. The risk of developing STDR increased among the GG genotype with raised HbA1C levels (OR = 1.960, 95% CI 1.076 to 3.570 and p = 0.028) and raised fasting blood sugar (OR = 1.016, 95% CI 1.000 to 1.034 and p = 0.056). AG genotype with extra-retinal ocular complications of diabetes showed a greater risk of developing STDR (OR = 5.143, 95% CI 1.388 to 19.052 and p = 0.014).

Conclusion: No association was observed between any of the genotypes of ICAM-1 K469E polymorphism and the development of STDR. GG genotype is associated with the development of STDR in the presence of elevated glycosylated hemoglobin levels and elevated fasting blood sugar levels. AG genotype with extra-retinal diabetic ocular complications has a greater chance of developing STDR. However, there was no difference between the three genotypes of ICAM-1 K469E polymorphism in predisposing to the development of STDR.