Evaluation of the Relationship Between Cytochrome P450 Polymorphisms and T2DM Risk

Abstract

Background: Recent studies have identified some genetic polymorphisms of CYP2C8 and CYP2D6 related to disease susceptibility. However, it has not been reported whether polymorphisms in CYP2C8 and CYP2D6 are associated with the risk of type 2 diabetes mellitus (T2DM). We designed a case-control study to evaluate the relationship between those CYP polymorphisms and T2DM risk. Methods: Four single nucleotide polymorphisms (SNPs) of CYP2C8 and CYP2D6 were genotyped from 512 patients and 515 healthy controls using Agena MassARRAY. The chi-square test was used to compare the differences in allele and genotype frequencies between the two groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis to evaluate the relationship between polymorphism and T2DM risk. Results: The results found that the rs1065852 in CYP2D6 was correlated with the T2DM risk in overall (A vs. G: OR = 1.22, 95% CI: 1.03–1.45, P = 0.024; AA vs.GG: OR = 1.46, 95% CI: 1.04–2.06, P = 0.031; AA-AG vs. GG: OR = 1.36, 95% CI: 1.04–1.79, P = 0.026; additive: OR = 1.21, 95% CI: 1.02–1.44, P = 0.027). Gender stratification analysis results demonstrated that the rs1065852 in CYP2D6 was related with an increased the risk of T2DM in male and age < 59 years old. However, no statistical significance relation was found between CYP2C8 SNPs and T2DM risk. Conclusions: This study revealed that CYP2D6 (rs1065852) could be potential genetic markers of susceptibility to T2DM. Further studies are required to confirm our findings.