# Genetic variants of CYP2C19 and CYP2C18 and their clinical implications in the Saudi population

## TL;DR

This study identifies 53 genetic variants in CYP2C19 and CYP2C18 among Saudis, revealing five common variants that may affect drug metabolism and support personalized medicine.

## Contribution

The study reports the first comprehensive analysis of numerous previously unmeasured CYP2C19 and CYP2C18 variants in the Saudi population.

## Key findings

- 53 out of 141 CYP2C19 and CYP2C18 genetic variants were detected in 374 Saudi participants.
- Five variants (rs7067866, rs7916649, rs4917623, rs12248560, rs11188072) showed high frequencies and potential clinical relevance.
- Four CYP2C18 variants were linked to the ultra-rapid CYP2C19 metabolizer phenotype.

## Abstract

At least 500 genetic polymorphisms associated with the CYP2C19 and CYP2C18 enzymes have been identified, yet few polymorphisms have been measured in the Saudi population. Therefore, this study was aimed at determining the frequencies of numerous unmeasured CYP2C19 and CYP2C18 genetic variations, and their clinical and pharmacological implications, in KSA.

A multicenter cross-sectional study was conducted to determine the frequency of 141 CYP2C19 and CYP2C18 genetic variants. Blood samples from 374 Saudi adults were genotyped. GenomeStudio software was used for genotype calling for all samples. Bioinformatics analyses were performed for variant annotation. We excluded the rs4244285 variant since our main objective was to determine the frequency of numerous unmeasured or poorly documented CYP2C19 and CYP2C18 genetic variants in KSA. Including rs12769205 mitigated the haplotype analysis concern. Both rs4244285 and rs12769205 are CYP2C19∗2 key variations linked to loss of function.

Of the 141 variants associated with the CYP2C19 and CYP2C18 genes measured in 374 participants, 53 were detected, and the other 88 were not detected. Five detected variants had high frequencies: rs7067866, rs7916649, rs4917623, rs12248560, and rs11188072. Several detected variants were associated with clinical effects and appeared to influence drug metabolism.

This study investigated the presence of many previously undescribed CYP2C19 and CYP2C18 genetic variants in the Middle Eastern population. Tens of previously unmeasured CYP2C19 and CYP2C18 variants were identified in the Saudi population. Our findings have potential to contribute to pharmacogenomics and personalized medicine, and to support clinical decision-making.

•Limited CYP2C19 and CYP2C18 polymorphisms have been measured in the Saudi population.•This multicenter study examined 141 genetic variants in 374 Saudis.•Of the 141 variants investigated, 53 were detected, including five highly prevalent functional variants.•Highly frequent variants have been associated with altered pharmacokinetics and pharmacodynamics of common drugs.•Four of the observed CYP2C18 variants in Saudis were associated with the ultra-rapid CYP2C19 metabolizer phenotype.

Limited CYP2C19 and CYP2C18 polymorphisms have been measured in the Saudi population.

This multicenter study examined 141 genetic variants in 374 Saudis.

Of the 141 variants investigated, 53 were detected, including five highly prevalent functional variants.

Highly frequent variants have been associated with altered pharmacokinetics and pharmacodynamics of common drugs.

Four of the observed CYP2C18 variants in Saudis were associated with the ultra-rapid CYP2C19 metabolizer phenotype.