Genetic Variants of CYP2C8 Gene Predisposition to Type 2 Diabetes Risk

Abstract

Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels due to insulin resistance or inadequate insulin secretion from pancreatic beta cells. The mitochondrial CYP2C8 gene, located on chromosome 10q24, encodes cytochrome P450 and spans 37 kb with nine exons. Genetic variants in this gene may influence T2DM susceptibility. Method: This study aimed to investigate the association between genetic polymorphisms in the CYP2C8 gene (rs1934953 and rs1934952) and the risk of T2DM in Iraqi patients. Blood samples were collected from 48 participants, including 24 T2DM patients and 24 healthy controls. DNA extraction, polymerase chain reaction (PCR), and sequencing were performed to analyze genetic variations. Statistical analysis was conducted using chi-square tests, logistic regression, and Hardy-Weinberg equilibrium calculations. Results: Analysis revealed that the rs1934953 variant in the CYP2C8 gene was associated with T2DM, with the A allele showing a protective effect (odds ratio: 0.840, 95% confidence interval: 0.780-0.904, P=3.04×10-6). Additionally, an interaction effect between rs1934953 in CYP2C9 and rs12766752 in CYP2C8 on T2DM risk was observed (P=0.003). Furthermore, rs1934953 showed significant association with high-density lipoprotein cholesterol (HDL-C). At the rs1934952 C/T locus, a transition type genetic mutation was detected, with the TT genotype considered a risk factor for T2DM, while the CC and CT genotypes were protective. The Hardy-Weinberg probability value for the patient group was 0.0321, indicating notable discrepancies in genotype distribution, while the healthy group showed no significant differences (Hardy probability: 0.2001). The TT genotype at rs1934953 was associated with a decreased risk of T2DM, while the CC and CT genotypes were potential risk factors. Conversely, at rs1934952, the CC and CT genotypes were protective against T2DM, while the TT genotype was associated with increased risk. Conclusion: in conclusion, the study indicates that there may be links between CYP2C8 gene variances and an increased chance of type 2 diabetes in Iraqi patients.