Association Between Diabetes Mellitus and Cytochrome P450 Family 2 Subfamily C Member 19 (CYP2C19) Loss-of-Function...

Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) loss-of-function (LOF) polymorphisms reduce the metabolic activation of clopidogrel and contribute to interindividual variability in antiplatelet response. Diabetes mellitus is associated with increased platelet reactivity and adverse cardiovascular outcomes; however, its association with CYP2C19 LOF allele carriage among patients undergoing coronary artery bypass grafting (CABG) remains incompletely understood.

This study aimed to evaluate the association between diabetes mellitus and CYP2C19 LOF allele carriage among patients undergoing CABG and to describe the distribution of CYP2C19 genotypes and metabolizer phenotypes in this population.

This analytical cross-sectional study included 100 consecutive patients undergoing elective CABG. CYP2C19 genotyping (*1, *2, *3, and *17 alleles) was performed using real-time polymerase chain reaction. LOF allele carriage was defined as the presence of at least one reduced-function allele (*2 or *3). Because platelet function testing was not performed, the study evaluated genetically predicted reduced clopidogrel metabolism rather than laboratory-confirmed clopidogrel resistance. Associations between diabetes mellitus and LOF allele carriage were examined using multivariable logistic regression adjusted for age, sex, smoking history, hypertension, and dyslipidemia.

The mean age of participants was 58.6 ± 9.3 years, and 72% were male participants. Overall, 46 of 100 patients (46.0%) carried at least one CYP2C19 LOF allele. LOF allele carriage was more common among patients with diabetes mellitus than among those without diabetes (58.0% vs. 34.0%; odds ratio (OR), 2.68; 95% confidence interval (CI), 1.19-6.02; p = 0.016). After adjustment for potential confounders, diabetes mellitus remained independently associated with LOF allele carriage (adjusted OR, 1.95; 95% CI, 1.04-3.65; p = 0.037). Other clinical variables, including age, sex, smoking history, hypertension, and dyslipidemia, were not significantly associated with LOF allele carriage.

In this cross-sectional study, diabetes mellitus was associated with a higher prevalence of CYP2C19 LOF allele carriage among patients undergoing CABG. Because platelet function testing was not performed, these findings reflect genetically predicted reduced clopidogrel metabolism rather than confirmed clopidogrel resistance. Larger prospective studies incorporating platelet function testing and clinical outcome assessment are required to confirm these findings and determine their clinical significance.