Polymorphism E23K (rs5219) in the KCNJ11 gene in Euro-Brazilian subjects with type 1 and 2 diabetes

Insulin secretion is regulated by ATP-sensitive potassium channels (KATP). The potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene, located on chromosome 11p15.1, encodes the subunit Kir6.2 that forms the pore region of KATP channels in pancreatic β-cells. Among the single nucleotide polymorphisms (SNPs) associated with KCNJ11, the E23K polymorphism (rs5219) promotes a substitution (G > A) of a glutamic acid residue for lysine at position 23. The E23K SNP has been associated with diabetes in several populations, although with controversial results. The aim of this study was to evaluate the association of the E23K SNP with type 1 and 2 diabetes in a case-control study approved by the Ethics Committee. We genotyped 458 Euro-Brazilian individuals, classified as healthy (control group, CTRL, N = 217), patients with type 1 diabetes mellitus (T1D, N = 102), and patients with type 2 diabetes mellitus (T2D, N = 139). Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using BanII restriction digestion. The restriction fragments were separated by polyacrylamide gel electrophoresis and visualized by ethidium bromide staining. The genotype (EE/EK/KK) frequencies (%) for the CTRL group (38.2/50.2/11.6), T1D (34.3/52.0/13.7), and T2D (38.2/48.9/12.9) were in Hardy-Weinberg equilibrium and there were no significant differences (CRTL vs T1D, P = 0.771; CRTL vs T2D, P = 0.937; T1D vs T2D, P = 0.831). The minor allele frequencies (MAF; K) for CTRL (37.0%), T1D (39.7%), and T2D (37.4%) were not different among the groups (P > 0.05). The MAF value for healthy subjects was similar to other Caucasian populations (34.5-37.5%). In summary, the E23K polymorphism (rs5219) was not associated with type 1 or 2 diabetes mellitus in the studied population.