Ten percent of North Spanish individuals carry duplicated or triplicated CYP2D6 genes associated with ultrarapid metabolism of debrisoquine

Bernal, María Luisa; Sinués, B.; Johansson, Inger; McLellan, Roman A.; Wennerholm, Agneta; Ingelman-Sundberg, Magnus

doi:10.1097/01213011-199910000-00013

Cited by 24 publications

(29 citation statements)

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“…Of the 360 volunteers, 30 (8.3%) were found to carry a duplicated functional CYP2D6 gene and were thus classified as UM. The results indicate that the prevalence of this allelic variant in the Southern Italian (Sicilian) population is similar to that in a Spanish population [22,23] . This is consistent with the more frequent distribution of CYP2D6 gene duplication in the Mediterranean area compared to Northern Europe and may be indicative of a north-south gradient of the frequency within Europe.…”

Section: Cyp2c9 Cyp2c19 and Cyp2d6supporting

confidence: 51%

Pharmacogenetics of drug-metabolizing enzymes in Italian populations

Serpe

Canaparo

Scordo

et al. 2014

Drug Metabolism and Personalized Therapy

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: Drug-metabolizing enzymes play a major role in the biotransformation and subsequent elimination of most drugs and xenobiotics from the body. Both phase I and phase II enzymes are highly polymorphic. Inter-individual differences in genes coding for drug-metabolizing enzymes are important for understanding variability in drug response and for individualization of drug prescription. The prevalence of genetic polymorphisms in drug metabolism varies widely with ethnicity, and marked differences in the distribution of allelic variants of genes encoding drug-metabolizing enzymes have been documented in populations of different racial origin. This review aimed to summarize the available studies on genetic polymorphisms associated with drug metabolism conducted in Italian populations and to compare the frequency of the various metabolizer phenotypes and most common variant alleles (and resulting genotypes) with corresponding values from other populations. Notably, published data are not extensive, and most studies were performed on relatively low numbers of individuals. In general, the frequency of polymorphisms in the cytochrome P450 ( CYP ) genes as well as in the investigated phase II enzymes in the Italian population was similar to values reported for other Caucasian populations. However, the prevalence of CYP2D6 gene duplication among Italians was found to be very high, confirming the higher frequency of CYP2D6 ultrarapid metabolizers in the Mediterranean area compared to Northern Europe. It is worth noting that a geographic gradient in the flavin-containing monooxygenase 3 polymorphism distribution was also seen, the Italian population showing higher similarity to other Mediterranean populations than to North Europeans.

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Section: Cyp2c9 Cyp2c19 and Cyp2d6supporting

confidence: 51%

Pharmacogenetics of drug-metabolizing enzymes in Italian populations

Serpe

Canaparo

Scordo

et al. 2014

Drug Metabolism and Personalized Therapy

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“…Available reports, however, suggest that the frequency of UMs varies among ethnic groups, with studies reporting low prevalence in some European white populations (0.8% in Denmark and Germany, 1.0% in Sweden) [ [23,24]. The highest frequencies of the UM phenotype are reported in Ethiopians (29%) [21] and Saudi Arabians (21%) [51].…”

Section: Um Phenotypementioning

confidence: 99%

“…The challenge is that individuals of European, African, and Hispanic ancestry have all emigrated from different regions that have different [20] to 29% in Ethiopians [21], and data on what proportion of African-Americans is of Ethiopian descent are lacking. Wide ranges in the prevalence of both the UM and PM phenotypes have also been reported in individuals of European descent (0.8%-10% and 1.5%-10%, respectively) [22][23][24][25].…”

Section: Incidence Of Cyp2d6 Phenotypesmentioning

confidence: 99%

Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications

et al. 2006

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After completing this course, the reader will be able to:1. List the four different genotypes for CYP2D6 polymorphism.2. Understand the potential effects of CYP2D6 polymorphism on the efficacy and safety for drugs metabolized via this enzyme.3. List the ethnic groups that are most frequently affected by genetic variation of the CYP2D6 enzyme. Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.

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“…Ultrarapid metabolizers are therefore at higher risk for therapeutic failures and might be at the risk for cardiovascular side effects when receiving a higher dosage (Brockmoller et al, 2007). (Dahl et al, 1992;Masimirembwa et al, 1993;Aklillu et al, 1996;McLellan et al, 1997;Sachse et al, 1997;Bathum et al, 1998;Yamada et al, 1998;Bernal et al, 1999;Griese et al, 1999;Wennerholm et al, 1999;Nishida et al, 2000;Ingelman-Sundberg and RodriguezAntona, 2005;Lopez et al, 2005;Lee et al, 2006;Menoyo et al, 2006;Sheng et al, 2007;Sistonen et al, 2007;Buzkova et al, 2008;Gaedigk and Coetsee, 2008). Frequency of CYP2D6 deletion in North America is given for both Caucasians and African Americans, the latter in brackets.…”

Section: Pharmacokinetics Of Antidepressants In Cyp2d6 Umsmentioning

confidence: 99%

CNVs of human genes and their implication in pharmacogenetics

Johansson

Ingelman‐Sundberg²

2008

Cytogenet Genome Res

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Pharmacogenetics encompasses genetic variation with importance for drug response and adverse drug reactions with emphasis on drug transporters, drug metabolizing enzymes, and drug receptors. The highest penetrance with respect to drug action is generally observed for variability in genes encoding drug metabolizing enzymes, and gene copy number variations play a very important role in this respect. Alleles containing 0–13 active gene copies have been described, and this variation affects the clinical outcome of treatment for about 20–30% of all drugs. Gene copy number variation has also an influence on nicotine metabolism and detoxification by glutathione transferases and sulfotransferases. In the current overview we provide an update of the situation with emphasis on clinically important examples.

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Ten percent of North Spanish individuals carry duplicated or triplicated CYP2D6 genes associated with ultrarapid metabolism of debrisoquine

Cited by 24 publications

References 0 publications

Pharmacogenetics of drug-metabolizing enzymes in Italian populations

Pharmacogenetics of drug-metabolizing enzymes in Italian populations

Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications

CNVs of human genes and their implication in pharmacogenetics

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