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Methods and Findings
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Methods Find Exp Clin Pharmacol 2000, 22(9): 695
ISSN 0379-0355
Copyright 2000 Clarivate Analytics
CCC: 0379-0355
DOI: 10.1358/mf.2000.22.9.802286
 
 
Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the colombian population
Isaza, C.A., Henao, J., Lopez, A.M., Cacabelos, R.
 
 
Cytochrome P450 2D6 monooxygenase metabolizes several commonly used drugs, particularly psychotropics and cardiovascular agents. The gene that encodes this isoenzyme is highly polymorphic, with 1-10% of the population carrying mutations that produce an inactive enzyme, and 1-29% of individuals who possess additional copies of functional CYP2D6 genes. The genotypic features of the CYP2D6 gene have already been studied in many ethnic groups; however, the genetic characteristics of this enzyme are unknown in the Colombian population. The allelic variants and mutations of this polymorphic isoenzyme are the main cause of interindividual and interethnic differences in the therapeutic efficacy and adverse effects at standard doses of drugs metabolized by the products of the CYP2D6 gene. In the present study we have isolated, sequenced and genotyped the CYP2D6 gene in the Colombian population. The distribution of allelic frequencies of 10 alleles associated with normal, diminished or increased CYP2D6 activity has been studied in 121 healthy volunteers. The commonest alleles detected in the Colombian people were the functional alleles *1 (38.8%) and *2 (37%). Among the seven nonfunctional alleles studied in our sample, we found frequencies of 19.4%, 1.6%, 1.2% and 0.8%, for the *4, *17, *3 and *5 alleles, respectively. The alleles *6, *7 and *8 could not be identified in any of the subjects studied. The frequency of the duplicate allele was 1.2%. In this Colombian sample, 91.7% of the individuals were normal metabolizers (EM), 6.6% were poor metabolizers (PM), and 1.7% were ultrarapid metabolizers (UM). These results show that the allelic distribution of the CYP2D6 gene in the Colombian population of mestizo-prevalent subjects is compatible with the genomic assembly of the constitutive tri-ethnic origin of this Latin American country.


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