High frequency of CYP2D6 ultrarapid metabolizers in Spain: controversy about their misclassification in worldwide population studies.
A high frequency (7-10%) of CYP2D6 ultrarapid metabolizers estimated from the genotype (gUMs) has been claimed to exist among Spaniards and Southern Europeans. However, methodological aspects such as the inclusion of individuals carrying non-active multiplied alleles as gUMs may have led to an overestimation. Thus, this study aimed to analyze the gUM frequency (considering only those carrying more than two active genes) in 805 Spanish healthy volunteers studied for CYP2D6*2, *3, *4, *5, *6, *10, *17, *35, *41, and multiplications. Second, all worldwide studies reporting gUM frequencies were reviewed in order to evaluate potential misclassifications. The gUM frequency in this Spanish population was 5.34%, but increased to 8.3% if all individuals with CYP2D6 multiplications were classified as gUMs without considering the activity of the multiplied alleles. Moreover, among all reviewed worldwide studies only 55.6% precisely determined whether the multiplied alleles were active. Present results suggest that the evaluation of CYP2D6 ultrarapid metabolism should be standarized, and that the frequency of gUMs should be reconsidered in Spaniards and globally.
CICAB Clinical Research Center, Extremadura University and Medical School, Badajoz, Spain.
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Naranjo
CICAB Clinical Research Center, Extremadura University and Medical School, Badajoz, Spain.
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F
de Andrés
CICAB Clinical Research Center, Extremadura University and Medical School, Badajoz, Spain.
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Delgado
CICAB Clinical Research Center, Extremadura University and Medical School, Badajoz, Spain.|Primary Health Care Center 'Ciudad Jardín', Badajoz, Spain.
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Cobaleda
CICAB Clinical Research Center, Extremadura University and Medical School, Badajoz, Spain.
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Peñas-Lledó
CICAB Clinical Research Center, Extremadura University and Medical School, Badajoz, Spain.|CIBERSAM, Instituto de Salud Carlos III, Madrid, Spain.
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LLerena
D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007700:Kinetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013030:Spain
D019389:Cytochrome P-450 CYP2D6