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CYP2D6 Genotype and Phenotype in Amerindians of Tepehuano Origin and Mestizos of Durango, Mexico

From the Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional del IPN Unidad Durango, CIIDIR-IPN, México (Ms Sosa-Macías, Dr Bradley-Alvarez, Ms Alanis-Bañuelos, Dr Lares-Asseff); Sección Externa de Toxicología del Centro de Investigación y de Estudios Avanzados del IPN, México (Dr Elizondo, Ms Sosa-Macías); Departamento de Farmacología, Torre de Investigación "Dr. Joaquín Cravioto" del Instituto Nacional de Pediatría-SSA, México (Ms C. Flores-Pérez, Ms J. Flores-Pérez, Dr Lares-Asseff).

Although the drug-metabolizing enzyme CYP2D6 has been studied extensively in subjects of differing ethnicities, limited CYP2D6 pharmacogenetic data are available for the Amerindian population and Mestizos of Mexico. Dextromethorphan hydroxylation phenotype was studied in Tepehuano Amerindian (n = 58) and Mestizo (n = 88) subjects, and 195 individuals (85 Tepehuano Amerindians and 110 Mestizos) were genotyped by polymerase chain reaction–restriction fragment length polymorphism methods to identify the frequencies of the CYP2D6*3, *4, *6, and *10 alleles. Tepehuano Amerindian subjects lacked the poor metabolizer (PM) phenotype, whereas in Mestizos the PM phenotype frequency was 6.8%. The CYP2D6*3, *6, and *10 alleles were not found in Tepehuano Amerindians. The CYP2D6*4 allele had a low frequency (0.006) in this Amerindian group. In the Mestizo group, the CYP2D6*3, *4, and *10 alleles had frequencies of 0.009, 0.131, and 0.023, respectively. The CYP2D6*6 allele was not found in Mestizos. The genotype-phenotype association was strongly statistically significant (r² = .45; P = .005) in Mestizos. The Tepehuano population was found to have a low phenotypic and genotypic CYP2D6 diversity and differed from other Amerindian groups. On the other hand, the frequencies of the CYP2D6 variant alleles in Mestizos were similar to those reported for whites.

Key Words: Allele frequency • CYP2D6 polymorphism • ethnic difference • Tepehuan Amerindians

Address for reprints: Ismael Lares-Asseff, MD, PhD, CIIDIR-IPN Unidad Durango. Laboratorio de Farmacogenómica y Biomedicina Molecular. Calle Sigma s/n Fracc. 20 de Noviembre II Durango, Dgo. México C.P. 34220.

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