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

The Pharmacogenomics Journal volume 16, pages 113–123 (2016)Cite this article

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Abstract

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.

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Acknowledgements

This study was supported by Gobierno de Extremadura, AEXCID 13IA001 (to SIFF) and coordinated by the network Red Iberoamericana de Farmacogenética y Farmacogenómica (http://www.ribef.com). Consejo Nacional de Ciencia y Tecnología de México (CONACyT; no. 167261). Some researchers were supported by fellowships from the University of Costa Rica (PhD fellowship to CCG in Spain), Gobierno de Extremadura, Consejería de Empleo, Empresa e Innovación and Fondo Social Europeo (FSE) (TE14002 to AD), Instituto de Salud Carlos III-Sara Borrell Postdoc Program (CD13/00348 to FdA), Brazilian Government CAPES grant (BEX 12350/2013-03 fellowship to FR-S and 110/2012) and from CONACYT (no. 369708 to IF-G).

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  1. CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain

    I Fricke-Galindo, C Céspedes-Garro, F Rodrigues-Soares, M E G Naranjo, Á Delgado, F de Andrés, E Peñas-Lledó & A LLerena

  2. Doctorate in Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico

    I Fricke-Galindo

  3. Genetics Section, School of Biology, University of Costa Rica, San José, Costa Rica

    C Céspedes-Garro

  4. Department of General Biology, Federal University of Minas Gerais, Belo Horizonte, Brazil

    F Rodrigues-Soares

  5. Department of Biological Systems, Metropolitan Autonomous University, Mexico City, Mexico

    M López-López

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Fricke-Galindo, I., Céspedes-Garro, C., Rodrigues-Soares, F. et al. Interethnic variation of CYP2C19 alleles, ‘predicted’ phenotypes and ‘measured’ metabolic phenotypes across world populations. Pharmacogenomics J 16, 113–123 (2016). https://doi.org/10.1038/tpj.2015.70

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