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Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer phenotype in five Amerindian groups and western Mestizos from Mexico.

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Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer phenotype in five Amerindian groups and western Mestizos from Mexico.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Salazar-Flores, Joel Torres-Reyes, Luis A. Martínez-Cortés, Gabriela Rubi-Castellanos, Rodrigo Sosa-Macías, Martha Muñoz-Valle, José F. González-González, César Ramírez, Angélica Román, Raquel Méndez, José L. Barrera, Andrés Torres, Alfredo Medina, Rafael Rangel-Villalobos, Héctor
Spatial Coverage	Mexico
Description	Author Affiliation: Salazar-Flores J ( Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara, Ocotlán, Jalisco, México.)
Abstract	BACKGROUND: The distribution of polymorphisms in the CYP2D6 and CYP2C19 genes allows inferring the potential risk for specific adverse drug reactions and lack of therapeutic effects in humans. This variability shows differences among human populations. The aim of this study was to analyze single-nucleotide polymorphisms related to a poor metabolizer (PM) phenotype in nonpreviously studied Amerindian groups and Mestizos (general admixed population) from Mexico. METHODS: We detected by SNaPshot(®) different polymorphisms located in CYP2D6 (3, 4, 6, 7, and 8) and CYP2C19 (2, 3, 4 and 5) in western Mestizos (n=145) and five Amerindian groups from Mexico: Tarahumaras from the North (n=88); Purépechas from the Center (n=101); and Tojolabales (n=68), Tzotziles (n=88), and Tzeltales (n=20) from the Southeast. Genotypes were observed by capillary electrophoresis. The genetic relationships among these populations were estimated based on these genes. RESULTS AND DISCUSSION: The wild-type allele (1) of both genes was predominant in the Mexican populations studied. The most widely observed alleles were CYP2C192 (range, 0%-31%) and CYP2D64 (range, 1.2%-7.3%), whereas CYP2D63 was exclusively detected in Mestizos. Conversely, CYP2C194 and 5, as well as CYP2D63, 6, 7, and 8, were not observed in the majority of the Mexican populations. The Tarahumaras presented a high frequency of the allele CYP2C192 (31%) and of homozygotes 2/2 (10.7%), which represent a high frequency of potentially PM phenotypes in this Amerindian group. The genetic distances showed high differentiation of Tarahumaras (principally for CYP2C19 gene). In general, a relative proximity was observed between most of the Amerindian, Mexican-Mestizo, and Latin-American populations. CONCLUSION: In general, the wild-type allele (*1) predominates in Mexican populations, outlining a relatively homogeneous distribution for CYP2C19 and CYP2D6. The exception is the Tarahumara group that displays a potentially increased risk for adverse reactions to CYP2C19-metabolized drugs.
File Format	HTM / HTML
ISSN	19450265
e-ISSN	19450257
DOI	10.1089/gtmb.2012.0055
Journal	Genetic Testing and Molecular Biomarkers
Issue Number	9
Volume Number	16
Language	English
Publisher	Mary Ann Liebert
Publisher Date	2012-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Genetics Discipline Molecular Biology Aryl Hydrocarbon Hydroxylases Genetics Cytochrome P-450 Cyp2d6 Indians, North American Polymorphism, Genetic Alleles Metabolism Cytochrome P-450 Cyp2c19 Gene Frequency Genotype Mexico Phenotype Polymorphism, Single Nucleotide Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical)

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Distribution of CYP2D6 and CYP2C19 Polymorphisms Associated with Poor Metabolizer Phenotype in Five Amerindian Groups and Western Mestizos from Mexico

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