Genetic Polymorphisms of SLC22A1 and CYP2C9 Genes in Patients with Type 2 Diabetes in Port Harcourt, Nigeria

Abstract

Background: Genetic variation in proteins involved in antidiabetic drug transport and metabolism may contribute to differences in type 2 diabetes mellitus (T2D) susceptibility and treatment response. Aim: To determine the genotype and allele distributions of selected CYP2C9 (rs1057910, rs1799853, rs41291560, rs9332214) and SLC22A1 (rs1220835, rs594709, rs622342) variants and to evaluate their associations with T2D among patients in Port Harcourt, Nigeria. Study Design: Analytical cross-sectional study was undertaken. Place and Duration of Study: Port Harcourt, Nigeria, and Inqaba Biotec, between November 2022 and April 2023. Methodology: Ninety subjects aged 18–70 years, of whom 54 were female and 26 were male, were recruited. Eight SNPs, four each from the SLC22A1 and CYP2C9 genes, respectively, were selected and genotyped using MassARRAY. Hardy–Weinberg equilibrium, genotype and allele frequencies, and their associations with T2D status were assessed using chi-square tests, odds ratios (ORs), and relative risks (RRs), with 95% confidence intervals; p < 0.05 was considered statistically significant. Results: CYP2C9 rs1057910, rs1799853, and rs41291560 and SLC22A1 rs1220835 were monomorphic in both groups, with all subjects carrying the wild-type genotype. The CYP2C9 rs9332214 variant showed no significant differences in genotype or allele frequencies between the T2D and control groups (p > 0.05). Among the SLC22A1 variants, the A allele of rs594709 was significantly less frequent in patients with T2D than in controls (81.67% vs 95.00%; χ² = 6.275, p = 0.012; OR = 0.234, 95% CI: 0.07–0.75), and the genotype distribution of rs622342 differed significantly between the groups (χ² = 5.000, p = 0.025), although the allele-level association was not significant (p = 0.130). Conclusion: Most CYP2C9 and SLC22A1 variants examined showed limited polymorphism in this population. However, SLC22A1 rs594709 and rs622342 showed evidence of associations with T2D, suggesting a possible contribution of OCT1 variants to T2D susceptibility in this Nigerian population; this finding warrants confirmation in larger, adequately powered studies.