Abstract
BACKGROUND. The ATP-sensitive K (KATP) channel regulates insulin sensitivity, by linking insulin secretion to changes in blood glucose levels. HYPOTHESIS. Kir6.2 is a specific point mutation in KCNJ11 gene, which encodes the pore-forming subunit of the pancreatic KATP channel, and was reportedly linked with impaired insulin secretion and diabetes development. METHODOLOGY. We investigated whether the E23K Kir6.2 polymorphism is associated with the presence of diabetic retinopathy (DR) in 804 Tunisian type 2 diabetes (T2DM) patients. Genotype analysis was performed by real-time PCR. MAJOR RESULTS. While the E23K minor allele frequency was comparable between T2DM patients with (DR) and without (DWR) retinopathy (32.3% vs. 31.9%; P = 0.919), the distribution of E23K genotypes was significantly different between both T2DM patient groups (P = 0.024). In T2DM patients with HbA1c values < 7.0%, the T/T genotype was present at higher frequency in DR (14.9%) than in DWR (4.3%) patients (P = 0.007). Regression analysis confirmed the association of Kir6.2 K/K genotype with DR in patients with normal HbA1c (P = 0.022; OR = 12.70; 95% CI = 1.46-10.25). CONCLUSIONS. The E23K Kir6.2 polymorphism is associated with DR in T2DM in an HbA1c-dependent manner, thereby suggesting that Kir6.2 E23K homozygosity may predict the extent of hyperglycemic control in DR patients.