CYP2C gene polymorphisms in North African populations.

Abstract

Background: Cytochrome P450 is a superfamily of genes generating hemoproteins that metabolize foreign chemicals as well as endogenous compounds, such as steroids. The human CYP2C genes (CYP2C8, CYP2C9, CYP2C18, CYP2C19) cluster on chromosome 10 and metabolize many clinically useful drugs. CYP2C19 and CYP2C9 have been the most studied while CYP2C8 has been studied less frequently. CYP2C18 has been relatively ignored until recently but its importance has begun to be recognized.

Methods and results: We studied the genotypes of 7 pharmacogenetic markers in 3 CYP2C genes: CYP2C19 (rs12248560), CYP2C9 (rs4918758, rs1799853), and CYP2C8 (rs10509681, rs11572103, rs1058930, rs11572080), in one Libyan population and 7 Tunisian populations. Five of the 7 SNPs are in exons and have functional consequences while one intronic SNP is considered to be in close proximity to a regulatory region because of the many studies that report associations with metabolic effects. We carried out principal component analysis (PCA) on the North African populations and 83 other populations from the 1000 Genomes Project and Kidd Laboratory. The geographic clustering observed via PCA was more pronounced when considering multi-SNP haplotype frequencies.

Conclusion: This study reveals the intermediate position of North Africans between Europeans and Asians and the varied dissimilarities with other world regions. The genetic variation observed within and between geographic regions have implications for drug metabolism and adverse individual responses to medical treatments.