title: Characterization of variant alleles of cytochrome CYP2D6 in a Spanish population.
abstract: The CYP2D6 gene codes for a P450 monooxygenase which is involved in the biotransformation of a large number of commonly prescribed drugs. Adverse drug effects and therapeutic failure can be related to abnormal CYP2D6 activity. We investigated the allele and genotype frequencies of cytochrome P4502D6 in a Spanish population to predict the prevalence of ultra-rapid and poor metabolizer phenotypes in our population and to design a feasible CYP2D6 genotyping protocol. The study included 105 healthy unrelated Spanish Caucasian volunteers. CYP2D6 genotyping was performed by a combination of long-PCR, direct sequencing and allele-specific real-time PCR. The frequency of the wild-type CYP2D6*1 allele was 31%. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity showed frequencies of 40.47, 2.38 and 1.90%, respectively. Frequencies of defective alleles *3, *4, *5 and *6 were 0.95, 13.8, 3.33 and 0.95%, respectively. The defective CYP2D6 alleles *7, *8, *12, *14, *15 and *21 were not found. Duplicated CYP2D6 alleles were detected at a frequency of 4.27%. Our protocol allows the identification of the four inactive CYP2D6 alleles (*3, *4, *5 and *6) and the detection of alleles with CYP2D6 *1, CYP2D6 *2 and CYP2D6*4 gene duplications. Testing for this reduced CYP2D6 allele set would facilitate its use in clinical practice by assisting in the development of individualized pharmacotherapy.
authors.affiliation: Servei de Genètica, Hospital de la santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Menoyo
authors.forename: Elisabeth
authors.initials: E
authors.lastname: del Rio
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D010599:Pharmacokinetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D015995:Prevalence; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D019389:Cytochrome P-450 CYP2D6