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


CONCLUSIONS
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.
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
Ana Miriam
AM
Saldaña-Cruz
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
Lilia Carolina
LC
León-Moreno
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
José
J
Sánchez-Corona
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
Daniel Alejandro Márquez-de
DA
Santiago
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
Francisco
F
Mendoza-Carrera
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
Xochitl Helga
XH
Castro-Martínez
2 Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara , Guadalajara, México .
Alejandra Guadalupe
AG
García-Zapién
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
María Cristina
MC
Morán-Moguel
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social , Guadalajara, México .
Silvia Esperanza
SE
Flores-Martínez
D000328:Adult; D000483:Alleles; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
CYP2C haplotypes; CYP2C19 alleles; CYP2C9 alleles; Mestizo population; Western Mexico