Background

Type 2 diabetes mellitus (T2DM) is a multifactorial disease and its prevalence has been rapidly increasing throughout the world which is associated with several gene polymorphisms. KCNJ11 gene encodes for the Kir6.2 subunit of the ATP-sensitive potassium channel in the pancreatic beta cell; thus, mutation in this gene cause impaired insulin secretion leading to T2DM.
Aim

To investigate the association between E23K polymorphism of KCNJ11 gene and T2DM in Bangladeshi population.
Method

The type of study was case-control; 200 unrelated subjects of 100 healthy controls and 100 diabetic patients were recruited (diagnosed based on American Diabetes Association criteria). The serum fasting glucose (FSG), HbA1C, insulin (INS) and lipid profiles were estimated by GOD-PAP, HPLC, ELISA and CHOD-PAP enzymatic colorimetry methods respectively. HOMAB% and HOMAS% were calculated by HOMA-SIGMA Software. Chemical method was used for DNA extraction. PCR-RFLP method was used to detect KCNJ11 E23K (rs5219) gene polymorphism with Ban II restriction enzyme digestion. Data were analyzed using independent t, Mann -Whitney U and Chi-square or Fisher exact test, as appropriate. p< 0.05 was considered as significant.
Results

A significant differences were shown in FSG (M±SD, mmol/L, Case vs Control, 7.5±2.6 vs 5.3±0.7; p<0.001) and HbA1c level (M±SD, %, Case vs Control, 7.9±1.7 vs 5.4±0.6; p<0.001) between two groups. INS level [Med (Min- Max), µIU/mL, Case vs Control. 18.62 (3.13-44.04) vs 12.85 (1.12-26.50), p<0.001] and beta cell secretory defect (HOMAB %, M±SD, Case vs Control, 128.4±79.7 vs 124.67±71.2, p=ns) were higher; and insulin sensitivity (HOMAS %, M±SD, Case vs control, 38.76±25.8 vs 69.9±46.5; p=0.002) was significantly lower in case compared to control respectively. Lipid profiles were also higher in case in comparison to control but HDL level showed a significant difference between two groups (M±SD, mg/dL control 43±12 Vs case 40±8; p<0.001). A statistically significant association was found in E23K heterozygous genotype between T2DM and control [p<0.0001, OR (95% CI)- 4.20 (2.27-7.80)]. However, no association was found in homozygous K23K genotype [p=1.000, OR (95% CI)-1.01 (0.28-3.67)]; whereas K alleles of cases were significantly higher than control [p<0.05, OR (95% CI) - 1.90 (1.40-3.20)] respectively. 
Discussion

In biochemical characteristics of T2D and control, a significant association among glucose, HbA1c and HDL level were found. KCNJ11 gene was analyzed for investigation of the association between E23K polymorphism with prevalence of T2DM. Li 1 found E23K contributed to T2D susceptibility. However, Wang et al. 2 did not found any relationship between the E23K and T2D. Our study showed that frequency of E23K genotype is significantly (p<0.0001) more in diabetic patients. UKPDS showed frequency of EK in T2D was a little higher than glucose tolerated people 3. Asaf et al 4 had shown the inheritance of the K allele predisposes for T2D. Moreover, we found that carriers of K allele have more risk for T2D (P <0.05) which showed the higher insulin level and lower sensitivity (p=NS) then E variant.  This finding correlates with Chistiakov et al (P = 0.023) and also characterized the loci for susceptibility to T2D and altered insulin secretion 5. From the obtained results, it can be concluded that KCNJ11 (E23K) gene polymorphism is associated with T2DM in Bangladesh.

References:

    Li YY. The KCNJ11 E23K gene polymorphism and T2DM in the Chinese Han population: A meta-analysis of 6,109 subjects. Mol Biol Rep. 2013;40:141–6.
    Wang GF, Jiang WJ et al. Correlation study of KCNJ11 gene E23K polymorphism with T2DM. Acta Acad Med. 2011;2:4–8.
    Gloyn AL, Hashim Y et al. Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with T2DM (UKPDS 53) Diabet Med. 2001;18:206–12.
    Asaf A, Ayesh BM, Hamdona OM. SNP-E23K of KCNJ11 gene and other risk factors associated with T2DM in Gaza. Int J Chem Life Sci. 2013;2:1146–52.
    Chistiakov DA, Potapov VA et al. The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2DM, glucose intolerance and altered insulin secretion in a Russian population. Diabetes Metab Syndr Clin Res Rev. 2008;2:185–91.

Association of SNP-KCNJ11 (E23K) gene with susceptibility to type 2 diabetes in Bangladeshi population