CYP2C9 and CYP2C19 Allele and Haplotype Distributions in Four Mestizo Populations from Western Mexico: An Interethnic Comparative Study

Genet Test Mol Biomarkers. 2016 Nov;20(11):702-709. doi: 10.1089/gtmb.2016.0115. Epub 2016 Sep 12.

Abstract

Aims: Polymorphisms in the CYP2C9 and CYP2C19 genes confer potential risk for specific adverse drug reactions and therapeutic effect failure. Their frequencies differ among ethnic groups. This study was aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mestizo populations from Western Mexico and their comparison with the reported data from other ethnic groups.

Methods: The CYP2C alleles (CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3) were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analyses using DNA samples from 477 healthy Mestizo individuals of Colima (n = 100), Jalisco (n = 147), Michoacán (n = 117), and Nayarit (n = 113).

Results: Frequencies ranged from 2.2-3.0% and 4.8-8.9% for CYP2C9*3 and CYP2C9*2 alleles, respectively, and 5.4-12.0% for CYP2C19*2, whereas the CYP2C19*3 allele was not found. Haplotype GACA, which harbors the loss-of-function allele CYP2C19*2, was the second most frequent (8.7%). Genetic heterogeneity between the Western Mexican populations studied here and the global population was evident (p < 0.05), except for most American populations and other Mexican Mestizo populations.

Conclusion: Our findings increase the evidence for genetic variability at relevant pharmacogenetic loci and could be useful in association studies involving drugs that are substrates for CYP2C enzymes in the Western Mexican population.

Keywords: CYP2C haplotypes; CYP2C19 alleles; CYP2C9 alleles; Mestizo population; Western Mexico.

MeSH terms

  • Adult
  • Alleles
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 CYP2C9 / metabolism
  • Ethnicity / genetics
  • Female
  • Gene Frequency
  • Genetics, Population
  • Genotype
  • Haplotypes
  • Humans
  • Indians, North American / genetics*
  • Male
  • Mexico
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19