IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 20, Issue 4 Ser.6 (April. 2021), PP 58-65 www.iosrjournals.org DOI: 10.9790/0853-2004065865 www.iosrjournal.org 58 | Page Association of E23K Genotypes to T2DM Complications in subjects in Port Harcourt City, Nigeria. Enyi, Alice Ruhuoma, Bresibe, Ngozi and Brown, Holy 1 1 Department of Medical Laboratory Science, Rivers State University, Npkolu, Port Harcourt, Nigeria Abstract This study examined the association between the E23K allele variant of the KCNJ11 gene with type 2 diabetes mellitus in a Nigerian population and the possible complications that may arise from the variant. The E23K polymorphism of the KCNJ11 gene results from a substitution of the amino acid lysine to glutamate at codon 23. This alteration causes a critical inhibition of glucose-induced insulin secretion thereby resulting in hyperglycaemia. Hundred consenting Nigerian adults (73 diabetics and 27 non-diabetic subjects) aged at least 40 participated in this study. Genotyping was carried out with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique using BanII restriction digestion enzyme. The restriction fragments were then electrophoresed on DNA grade agarose gel and the bands visualised using a UV transilluminator. The genotypes identified are the EE (150bp band), EK (150bp+178bp bands) and KK (178bp band) genotypes. The KK genotype was preponderant in the diabetic participants (52%) and was followed by the EK genotype (25.9%) while the EE genotype was more in the non-diabetic participants (66.7%). The risks conferred by the different genotypes/allele are as follows: EK (p value = 0.5639; OR = 1.32), EE (p value = 0.000; OR = 0.21), KK (p value = 0.0037; OR = 7.03), K (p value = 0.211; OR = 2.59) and E (p value = 0.0552; OR = O.52). A carrier of the KK genotype is seven times more likely than a non-carrier to develop type 2 diabetes mellitus (p value = 0.0037; 7.03). Only the KK genotype was found to significantly increase the risk of developing type 2 diabetes complications (p value = 0.02; OR = 12.67). The p values of the selected biochemical variables are as follows: leptin = 0.95, fasting blood sugar = 0.15, C-peptide = 0.47, Cystatin C = 0.86, HbA1C = 0.01, insulin = 0.65 and HOMA = 0.65. Of the glycaemic variables analyzed, only HbAlc showed a significant difference between the diabetic and control groups (p value = 0.01) but there was no significant difference in its levels in the different genotypes (p value = 0.64). A significant association between the E23K polymorphism and T2DM as well as complications that could arise from the disease was found in the Nigerian population that was studied. The KK genotype of the E23K polymorphism of the KCNJ11 gene is an independent predictor of Type 2 diabetes mellitus. Keywords: Diabetes, Complications, E23K, Polymorphism, KCNJ11 gene --------------------------------------------------------------------------------------------------------------------------------------- Date of Submission: 02-04-2021 Date of Acceptance: 16-04-2021 --------------------------------------------------------------------------------------------------------------------------------------- I. Introduction The proportion of people with type 2 diabetes is increasing in most countries with 79% of adults with diabetes living in low and middle income countries (International Diabetes Federation Atlas, 2017). The current prevalence rate of T2DM in Nigeria is not known but estimates place it in the region of 8-10% (Ogbera et al., 2014). A 2003 study by Nyenwe et al., yielded a crude prevalence rate of 6.8% and a standardized prevalence rate of 7.9% of T2DM in Port Harcourt. All regions of the country (even rural settlements) have been affected but the highest prevalence is seen in Southern Nigeria (Uloko et al., 2018). Genetic factor has been implicated as a driving force for the current prevalence rate. Several genetic association studies and genome-wide association scans (GWAS) have been carried out in a bid to identify susceptibility genes and loci associated with this disease (Assman et al., 2014). Some susceptibility genes identified by these genetic studies include TCF7L2 (Nanet et al., 2015), PPARG (Engwa et al.,2018), SLC30A8, HHEX/IDE (Saxena et al., 2007), CDKAL1, CDKN2A/B, IGF2BP2 and FTO (Scott et al.,2007), IRSI,ADAM TS9 and GCKR ( Bossegard et al.,2009), WFS1 (Sandhu et al.,2007), HNF1B (Sparoso et al.,2008) and KCNJ11 (Lasram et al.,2014). The KCNJ11 gene is found on chromosome 11 and codes for a 390 amino acid protein that is one of the subunits of the pancreatic K ATP channel ( Rastegari et al., 2015). Several single nucleotide polymorphisms (SNP) have been shown to increase susceptibility to type 2 diabetes mellitus. Thus far KCNJ11 has been found to have 219 SNPs, six of which have been linked to type 2 and they are: rs5219 (E23K polymorphism), rs5215, rs5210, rs5218, rs886288, rs2285676 (Haghvirdiazadeh et al., 2015). Studies on the full mutational mechanisms are incomplete and not yet comprehensively categorical