Global Distribution of CYP2C19 Risk Phenotypes Affecting Safety and Effectiveness of Medications

Abstract

Background: Genetic variability of CYP2C19 may affect safety or effectiveness of many drugs as outlined in the CPIC dosing guidelines. Aim was to determine the predictive prevalence of high-risk phenotypes due to CYP2C19 variants collectively in the world population. It was also aimed to establish a correlation how the identified high-risk phenotypes may affect safety or effectiveness of drugs. Methods: Frequency of CYP2C19*2, *3 and *17 alleles were obtained from 1000 Genomes project Phase III in line with Fort Lauderdale principles. Phenotypes were assigned using international standardized consensus terms based on the carrier of characteristics alleles. The CYP2C19 pharmacogenomics information of drugs were obtained from international pharmacogenomics working groups. Association of predicted high-risk phenotypes with the safety or effectiveness of medications were gained from CPIC dosing guidelines. Findings: Following CPIC dosing guidelines, ultrarapid metabolizers and poor metabolizers were considered as being as high-risk phenotypes for at least ten clinically important medications. Meta-analysis of the prevalence of high-risk phenotypes showed that it was statistically significant ( P <0.0001) in different ethnic groups with pooled prevalence of 27.4% (95% CI 18%-37%). The present study suggests that African (37.2%; 95% CI 34%-41%) and European (35.4%; 95% CI 31%-40%) population are being at particularly higher risk of either sub therapeutic drug responses or toxicities. Interpretation: Approximately one third of the world population were predictively identified as being as high-risk phenotypes affecting safety or effectiveness of certain number of medications. Large scale clinical studies are warranted to assess clinical outcomes of these medications considering CYP2C19 pharmacogenomics effects. Funding Statement: The author stated there was no funding. Declaration of Interests: The author declares no conflict of interest. Ethics Approval Statement: Not required.