title: Influence of CYP2D6 deletion, multiplication, -1584C-->G, 31G-->A and 2988G-->a gene polymorphisms on dextromethorphan metabolism among Mexican tepehuanos and mestizos.
abstract: The aim of this study was to explain the variability of CYP2D6 activity by the identification of CYP2D6 deletion and multiplications, and the single-nucleotide polymorphisms (SNPs) -1584C-->G, 31G-->A and 2988G-->A in Mexican Mestizo and Tepehuano subjects. One hundred twelve Mestizos and 99 Tepehuano Amerindians were studied, who were previously phenotyped with dextromethorphan. The frequencies of CYP2D6*2A [-1584C-->G] and *35 [-1584C-->G, 31G-->A] were 10.7 and 4.1%, respectively, in Mestizos, which is evidently a trend towards an extensive metabolism in carriers of the -1584G change. In Tepehuanos, *2A was identified with a frequency of 20%, and the allele *35 was not found. The frequencies of CYP2D6*5 (deletion) and *41[2988G-->A] were 1.3 and 2.2% in Mestizos and 0.5 and 1% in Tepehuanos, respectively. The SNP 2988A was found to be significantly related with the intermediate metabolizer phenotype in Mestizos (R = 0.309; n = 88; p = 0.006). The multiplications had frequencies of 4.1% in Mestizos and 1.5% in Tepehuanos. Only in the Mestizos did the presence of multiplications significantly decrease the DM/DX (dextromethorphan/dextrorphan) values (R = 0.273; n = 88; p = 0.016). The polymorphisms studied had different frequencies between Tepehuanos and Mestizos (p < 0.001); however, in the Tepehuano group these had a low influence on their phenotypic expression. It helps to understand the genotype-phenotype relationships of CYP2D6 in our studied populations.
authors.affiliation: Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional del IPN Unidad Durango, Durango, México.
authors.forename: Martha
authors.initials: M
authors.lastname: Sosa-Macías
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Alanis-Bañuelos
authors.forename: Adrián
authors.initials: A
authors.lastname: Llerena
authors.forename: Ismael
authors.initials: I
authors.lastname: Lares-Asseff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D003915:Dextromethorphan / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007198:Indians, North American; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6