CYP2D6 polymorphism in a Mexican American population.
BACKGROUND
Pharmacogenetic data are largely unavailable for Mexican Americans, despite being one of the largest populations in America.


METHODS
The CYP2D6 genotype (n = 349) and dextromethorphan hydroxylation phenotype (n = 285) were studied in 380 Mexican American subjects from Los Angeles County.


RESULTS
The allelic frequency was 22.8% for CYP2D6*2, 10.3% for CYP2D6*4, 7.4% for CYP2D6*10, 2.3% for CYP2D6*5, 1% for CYP2D6*XN (duplication), and <1% for CYP2D6*3 and CYP2D6*17. By using the published antimode for Caucasians, we identified nine subjects as poor metabolizers, an incidence of 3.2%. Of the eight poor metabolizers who were also genotyped, five either were homozygous for the CYP2D6*4 allele (4 cases) or had a combination of CYP2D6*4 and CYP2D6*5 alleles. The mean log(10) dextromethorphan/dextrorphan ratio was -2.47 for those classified as extensive metabolizers. The number of functional alleles among the extensive metabolizers correlated strongly with the phenotype, suggesting a gene-dose effect.


CONCLUSIONS
Compared with previous reports on Caucasian populations, studies show that Mexican Americans appear to possess a lower rate of CYP2D6*4. Frequencies for the other alleles appear to be less divergent between the two groups. This genotypic pattern might be responsible for the lower rate for the poor metabolizer status, as well as for the faster enzyme activity in the extensive metabolizer subjects that was also reflected in our data.
Mendoza
R
R
Department of Psychiatry, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Wan
Y J
YJ
Poland
R E
RE
Smith
M
M
Zheng
Y
Y
Berman
N
N
Lin
K M
KM
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000996:Antitussive Agents / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003915:Dextromethorphan / Q000493:pharmacokinetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D008970:Molecular Weight; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*
D000996:Antitussive Agents; D003915:Dextromethorphan; D004247:DNA; D019389:Cytochrome P-450 CYP2D6