Association of ICAM-1 Gene Polymorphisms with Diabetic Retinopathy in T2DM Patients from Northern India: Case-control and meta-analysis

BACKGROUND Diabetic retinopathy (DR) is a leading cause of vision loss in working-age adults, with prevalence varying by population and reaching ~ 34% in northern India. DR arises from chronic hyperglycemia–driven oxidative stress, inflammation, and microvascular dysfunction. Intercellular adhesion molecule-1 (ICAM-1) is central to leukocyte adhesion and retinal vascular injury; circulating ICAM-1 is elevated in patients and experimental models. Genetic variants in ICAM-1, notably c.1405A>G (rs5498) and c.721G>A (rs1799969), have been examined as risk markers for microvascular complications. Yet associations with DR are inconsistent across ethnicities, and robust data from northern India are limited, underscoring the need for population-specific studies. AIM To determine the association of ICAM-1 gene polymorphisms with DR in patients with type 2 diabetes mellitus (T2DM) from northern India. METHODS The present study included 614 participants: 302 patients with T2DM and DR and 312 patients with T2DM but without DR. The ICAM-1 polymorphism c.1405A>G (rs5498) was analyzed using PCR-restriction fragment length polymorphism, and analysis of c.721G>A (rs1799969) was done using the amplification-refractory mutation system. Further, approximately 10% of samples were validated for both polymorphisms for the observed genotypes by Sanger sequencing. A meta-analysis incorporating nine studies (1844 DR cases and 1595 controls) was also performed to assess the association of ICAM-1 rs5498 with DR risk. RESULTS The allele frequency and genotype distribution of ICAM-1 c.1405A>G polymorphism in the DR and control groups were not significant (P = 0.070 and P = 0.120, respectively). The GG genotype revealed a 1.6-fold increased risk of developing retinopathy (odds ratio = 1.61, 95% confidence interval: 1.01-2.58, P = 0.044). However, the AG genotype did not show any significant association (P = 0.643) between DR cases and controls. With c.721G>A in ICAM-1 the onset and progression of retinopathy was not found to be significantly correlated. The meta-analysis revealed no significant association between rs5498 and DR risk in the overall population or in Asians, but a significant association was observed in Caucasians under the allelic and recessive models. CONCLUSION The ICAM-1 rs5498 GG genotype increased retinopathy risk 1.61-fold in northern Indians. Meta-analysis of nine studies found no Asian association; a Caucasian signal warrants caution given limited subgroups and heterogeneity.