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

Abstract

ABSTRACT. 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 2 S.W. Souza et al. Genetics and Molecular Research 16 (2): gmr16029543(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.

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

“…Qiu et al confirmed that the rs5219 polymorphism of KCNJ11 predisposes to T2DM, mostly in Caucasians [ 93 ]. On the other hand, Souza et al demonstrated that the same polymorphism E23K (rs5219) was not associated with type 1 or 2 diabetes mellitus in Euro-Brazilian subjects [ 94 ]. A meta-analysis performed by Qin, L.J.…”

KATP Channel Expression and Genetic Polymorphisms Associated with Progression and Survival in Amyotrophic Lateral Sclerosis

“…These associations were not significant in patients with spinal onset, which implies a role for the K ATP channel in tissue susceptibility to cell loss and ALS pathogenesis. Three of the bulbar-onset ALS patients with rs4148646 G/G and rs5219 [29,[58][59][60]. The association of these two variants with a longer survival time in bulbar ALS patients may be related to the role of the K ATP channel in the control of microglia-mediated inflammatory processes.…”

Distribution of E23K Genotypes in Diabetic and Non-Diabetic Subjects in Port Harcourt metropolis, Nigeria.

“….5) showed that only HbAlc had a significant difference (p value =0.01). Leptin (p value = 0.95), C-peptide (p value = 0.47), cystatin C (p value = 0.86), insulin (p value = 0.65) and HOMA (p value = 0.65) were not statistically significant Souza et al, (2017). found that HbAlc medians were significantly higher in T2DM patients than the control group (p value = 0.001).…”