ANRIL polymorphism rs1333049, a novel genetic predictor for diabetic retinopathy complication

The 9p21 ANRIL (antisense non-coding RNA in INK4 locus) polymorphisms had reported association with type 2 diabetes mellitus (T2DM) and its induced macro/microvascular complications. However, the ANRIL single nucleotide polymorphism (SNP) rs1333049 has never been studied for its role in diabetic retinopathy; we therefore assessed its role in Pakistani population suffering from diabetes-induced retinopathy. The rs1333049 was genotyped in 806 individuals including 504 T2DM cases [206 patients without retinopathy (DNR) and 298 with retinopathy (DR) (non-proliferative DR (NPDR):147; proliferative DR (PDR): 151)] and 302 unaffected controls using allele-refractory mutation system (ARMS) polymerase chain reaction (PCR). The statistical analysis including genetic power estimation, χ2 test and Fisher's exact test were performed for the studied panel. Genetic power estimation showed that 504 T2DM cases and 302 controls had > 80% power to detect the association between ANRIL rs1333049 variant and diabetes patients with retinopathy in Pakistani population. An association was found between rs1333049 CC genotype and T2DM [χ2 = 13.9 (p = 0.0015); recessive model (RM): odds ratio (OR) = 2.36, 95% confidence interval (95%CI) = 1.42-3.95, p = 0.001], DNR [χ2 = 14.2 (p = 0.00081); RM: p = 0.001, OR = 2.66, 95%CI = 1.48-4.79, dominant model (DM): p = 0.02 OR = 1.68, 95%CI = 1.07-2.63], DR: (χ2 = 6.5, p = 0.0381; OR = 2.16, 95%CI = 1.23-3.79, p = 0.006), NPDR (χ2 = 4.25, p = 0.03; OR = 2.02, 95%CI = 1.03-3.96, p = 0.03) and PDR (χ2 = 8.11, p = 0.02; OR = 2.29, 95%CI = 1.19-4.39, p = 0.01) when compared with the healthy control subjects. The minor allele C was found to be associated with T2DM (OR = 1.32, 95%CI = 1.07-1.63, p = 0.009) and DNR (OR = 1.49, 95%CI = 1.15-1.94, p = 0.002). The ANRIL rs1333049 CC genotype is found to have a pathogenic role in the onset of T2DM and its induced retinopathy complication.