Influence of CYP2D6 deletion, multiplication, -1584C-->G, 31G-->A and 2988G-->a gene polymorphisms on dextromethorphan metabolism among Mexican tepehuanos and mestizos

Pharmacology. 2010;86(1):30-6. doi: 10.1159/000314334. Epub 2010 Jun 30.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Dextromethorphan / metabolism*
  • Female
  • Gene Deletion
  • Gene Duplication
  • Gene Frequency
  • Genotype
  • Humans
  • Indians, North American*
  • Male
  • Mexico
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*

Substances

  • Dextromethorphan
  • Cytochrome P-450 CYP2D6