47-PUB: Association between Cytochrome P450 Polymorphism and Type 2 Diabetes

Introduction and Objective: Type 2 diabetes (T2D) can influence cytochrome P450 (CYP450) enzyme activity through multiple mechanisms, beyond the contributions of hyperglycemia, insulin resistance, and β-cell dysfunction. The association between CYP450 polymorphism (CYP1A2, CYP2D6, CYP2C9, and CYP2C19) and T2D was investigated. Methods: T2D (n=942) and nondiabetic controls (n=380) were enrolled in this study. Genomic DNA was extracted and genotyped by AxiomTM genotyping array. Sixty-nine SNPs of CYP1A2, CYP2D6, CYP2C9, and CYP2C19 passed the Hardy-Weinberg equilibrium (HWE) test and were analyzed by binary logistic regression. Results: T2D had significantly older age, higher body mass index (BMI), and HbA1c but lower directed LDL-C levels than nondiabetic controls. Our study demonstrated that individuals with homozygous mutant for all eight SNPs [rs12768009 (G>A): OR=1.698, 95% CI=1.026-2.809; rs12769205 (A>G): OR=1.961, 95% CI=1.110-3.464; rs4986894 (T>C): OR=1.883, 95% CI=1.075-3.300; rs4244285 (G>A): OR=1.883, 95% CI=1.075-3.300; rs28399513 (T>A): OR=1.797, 95% CI=1.034-3.124; rs12571421 (A>G): OR=1.886, 95% CI=1.076-3.304; rs4417205 (C>G): OR=1.814, 95% CI=1.043-3.155 and rs12767583 (C>T): OR=1.899, 95% CI=1.083-3.328] of CYP2C19 had an increased risk of type 2 diabetes after adjustment for age and BMI. The minor alleles of rs12769205, rs4986894, rs4244285, rs12571421, rs4417205, and rs12767583 were significantly associated with T2D. Additionally, patients with heterozygous genotypes of rs12769205, rs4986894, rs4244285, rs28399513, rs12571421, rs4417205, and rs12767583 had significantly higher HbA1c levels compared to those with homozygous wildtype genotypes (all P-values < 0.05). Conclusion: The CYP2C19 polymorphisms showed a significant association with T2D in Thai patients. This study suggests that the CYP2C19 genotype may be used to improve precision in assessing the risk of T2D in the future. Disclosure W. Tangjittipokin: None. N. Teerawattanapong: None. S. Suthon: None. T. Narkdontri: None. S. Innang: None. S. Songlilitchuwong: None. N. Thowprasert: None. N. Chookruvong: None. P. Sukhoyachai: None. P. Prayoonkiet: None. N. Plengvidhya: None. Funding Mahidol University