Pharmacogenomic Insights: The Role of CYP2D6 Allelic Variants in Drug Metabolism Among COVID-19 Patients With Comorbidities.

BACKGROUND/AIM: Drug metabolism and thus drug efficacy can be affected by individual differences in cytochrome P450 2D6 enzyme (CYP2D6) due to genetic polymorphism in its gene. In this study, we aimed to investigate CYP2D6 allelic variants in drug metabolism among patients with COVID-19 with comorbidities.

PATIENTS AND

METHODS

This prospective case-control study, approved by the Pamukkale University Ethics Committee, investigated CYP2D6 polymorphisms (*4, *5, *7, *10) and COVID-19 outcomes in the Emergency Department between April and June 2020. Genomic DNA was extracted from whole blood, and genotyping was performed by polymerase chain reaction followed by sequencing on the ABI PRISM 7700 platform. Statistical analyses, including Student's t-test, Mann-Whitney U-test, chi-square test, and Fisher's exact test, were performed for laboratory and clinical data comparing between wild-type and heterozygous variants, and significance was determined as p<0.05. Data visualization was performed using SankeyMATIC, STATA 16.1 SE, and GraphPad Prism 5.0.

RESULTS

Among the 99 patients, 71 were identified as having one or more comorbid conditions. Comorbidity analysis showed that the absence of comorbidities was most common in CYP2D6*4 (38.46%), *5 (40%), and *7 (29.63%) heterozygotes, while hypertension and diabetes were also common. CYP2D6*10 heterozygotes (n=3) presented with cardiovascular diseases, osteomalacia, and arrhythmia. In particular, CYP2D6*5 heterozygotes had significantly lower lymphocyte counts. A trend toward differences was observed for hemoglobin in CYP2D6*4 and platelet count for CYP2D6*5 and CYP2D6*10, but these were not statistically significant.

CONCLUSION

This study highlights the diverse clinical profiles of COVID-19 patients with different CYP2D*6 variants, particularly the association between CYP2D6*5 heterozygosity and a reduced lymphocyte count.