Interethnic variation of CYP2C19 alleles, ‘predicted’ phenotypes and ‘measured’ metabolic phenotypes across world populations

• Published in: The pharmacogenomics journal Vol. 16; no. 2; pp. 113 - 123
• Main Authors: Fricke-Galindo, I, Céspedes-Garro, C, Rodrigues-Soares, F, Naranjo, M E G, Delgado, Á, de Andrés, F, López-López, M, Peñas-Lledó, E, LLerena, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2016; Nature Publishing Group
• Subjects: 45; 45/77; 631/208/721; 692/53/2423; Alleles; Biomedical and Life Sciences; Biomedicine; Continental Population Groups; CYP2D6 protein; Cytochrome P-450; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2C19 - metabolism; Cytochrome P450; Drug metabolism; Ethnicity; Gene Expression; Gene Frequency; Genetic aspects; Genetic drift; Genotype; Genotype & phenotype; Genotypes; Geography; Health aspects; Human Genetics; Humans; Identification and classification; Metabolism; Minority & ethnic groups; Oncology; Pharmacotherapy; Phenotype; Phenotypes; Polymorphism, Single Nucleotide; Population genetics; Population studies; Properties; Psychopharmacology; review
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2015.70

The present study evaluates the worldwide frequency distribution of CYP2C19 alleles and CYP2C19 metabolic phenotypes (‘predicted’ from genotypes and ‘measured’ with a probe drug) among healthy volunteers from different ethnic groups and geographic regions, as well as the relationship between the ‘predicted’ and ‘measured’ CYP2C19 metabolic phenotypes. A total of 52 181 healthy volunteers were studied within 138 selected original research papers. CYP2C19*17 was 42- and 24-fold more frequent in Mediterranean-South Europeans and Middle Easterns than in East Asians ( P <0.001, in both cases). Contrarily, CYP2C19*2 and CYP2C19*3 alleles were more frequent in East Asians (30.26% and 6.89%, respectively), and even a twofold higher frequency of these alleles was found in Native populations from Oceania (61.30% and 14.42%, respectively; P <0.001, in all cases), which may be a consequence of genetic drift process in the Pacific Islands. Regarding CYP2C19 metabolic phenotype, poor metabolizers (PMs) were more frequent among Asians than in Europeans, contrarily to the phenomenon reported for CYP2D6. A correlation has been found between the frequencies of CYP2C19 poor metabolism ‘predicted’ from CYP2C19 genotypes (gPMs) and the poor metabolic phenotype ‘measured’ with a probe drug (mPMs) when subjects are either classified by ethnicity ( r =0.94, P <0.001) or geographic region ( r =0.99, P =0.002). Nevertheless, further research is needed in African and Asian populations, which are under-represented, and additional CYP2C19 variants and the ‘measured’ phenotype should be studied.