Role of ADIPOQ Gene Variants in the Susceptibility to Diabetic Retinopathy in North-West Indian Population

Abstract

Diabetic retinopathy (DR) is the leading cause of vision loss and a major microvascular complication of type 2 diabetes (T2D). Adiponectin, an adipocyte-derived protein with anti-inflammatory and insulin-sensitizing effects is reduced in T2D and related metabolic disorders. The ADIPOQ gene has been implicated in T2D susceptibility, but its role in DR remains insufficiently understood. This study investigated the association of three ADIPOQ polymorphisms (rs266729, rs17300539 and rs17846866) with DR in a North-West Indian population. We analyzed 207 DR patients and 274 age- and gender-matched controls (>50 years). Genotyping was performed using PCR– restriction digestion (rs266729, rs17300539) and ARMS-PCR (rs17846866). Allele/genotype distributions were compared by chi-square test. Haplotypes were inferred using Haploview and gene– gene interactions were evaluated by multifactor dimensionality reduction (MDR). All three SNPs conformed to Hardy–Weinberg equilibrium in controls (p>0.05). The minor allele frequencies of rs17300539 and rs17846866 were significantly higher in DR cases than controls (both p<0.001). Under a dominant model, rs266729 (p=0.012, OR=1.66, 95% CI 1.12–2.48), rs17300539 (p<0.001, OR=4.59, 95% CI 2.17–9.71) and rs17846866 (p=0.001, OR=2.30, 95% CI 1.38–3.80) were associated with increased DR risk. Haplotype analysis revealed a protective effect of the G-C-T haplotype (p<0.001, OR=0.52, 95% CI 0.39–0.66). MDR analysis further supported significant SNP–SNP interactions (p=0.001). Our findings demonstrate a strong association of three ADIPOQ variants with DR in the North West Indian population. These variants may contribute to genetic susceptibility and could serve as potential biomarkers for early identification of highrisk individuals.