Frequencies of CYP2C9 polymorphisms in a Syrian cohort

The cytochrome P450 family 2 subfamily C member 9 (CYP2C9) exhibits extensive genetic variability that may influence the metabolism of approximately 16-20% of all drugs. Understanding the frequency and functional impact of the CYP2C9 variants is crucial for the implementation of pharmacogenetics. Our study aims to determine the frequencies of CYP2C9 variants in the Syrian population, contributing to the limited information available for Middle Eastern populations.

One hundred thirty-eight unrelated individuals from two major Syrian cities (Damascus and Homs) enrolled in this cross-sectional study. Genomic DNA was extracted from peripheral blood and specific PCR amplification products were purified and sequenced. The length of the amplicons allowed for the detection of 17 star alleles (i.e. *2, *8, *14, *20, *26, *33, *40, *41, *42, *43, *45, *46, *62, *63, *72, *73, and *78) in exon three, and seven star alleles (i.e., *3, *4, *5, *24, *55, *66, *68) in exon seven, in addition to two intronic variants. The frequencies of the functionally compromised CYP2C9*2^rs1799853 and CYP2C9*3^rs1057910 alleles were compared to same variants in other populations.

Of the 24 exonic alleles investigated, only the *2, *3, *41, and *46 alleles were detected at frequencies of 14.8%, 8.3%, 1.45%, and 0.72%, respectively, with 43.5% of the study subjects carrying at least one dysfunctional variant. The genotype frequencies observed were as follows: *1/*1 (56.5%), *1/*2 (23.9%), *2/*2 (0.7%), *3/*1 (12.3%), *2/*3 (4.3%), *3/*3 (0%), *1/*41 (0.7%), *2/*41 (0%), *3/*41 (0.7%), *1/*46 (0.7%), *46/*2 (0%), and *46/*3 (0%). Moreover, frequencies of the rs933120 and rs933119 intronic alleles were 12.3% and 6.1%, respectively. A high linkage disequilibrium (LD) was found (D'=0.78) between the intronic rs933119 and exonic rs1799853 (*2 allele).

This study provides evidence for high prevalence of the CYP2C9 *2 and *3 alleles, and consequently the intermediate and poor metabolizer phenotypes in Syrians. Two rare putative function-relevant variants (*41 and *46) were detected in three individuals. These findings pave the path to the efforts for implementing CYP2C9 pharmacogenetics-based personalized pharmacotherapy in this Middle Eastern population.