Sökning: WFRF:(Petzold Max 1973)
> (2005-2009)
> Ferreira P E >
Pharmacogenomics of...
Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam.
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- Veiga, M I (författare)
- Karolinska Institutet
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- Asimus, Sara, 1976 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Ferreira, P E (författare)
- Karolinska Institutet
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Martins, J P (författare)
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- Cavaco, I (författare)
- Karolinska Institutet
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Ribeiro, V (författare)
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Hai, T N (författare)
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- Petzold, Max, 1973 (författare)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för nationalekonomi med statistik, Statistiska forskningsenheten,Department of Economics, Statistical Research Unit
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- Björkman, A (författare)
- Karolinska Institutet
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- Ashton, Michael, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Gil, J P (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2008-11-01
- 2009
- Engelska.
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Ingår i: European journal of clinical pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 65:4, s. 355-63
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Abstract
Ämnesord
Stäng
- AIM: The aim of this study was to obtain pharmacogenetic data in a Vietnamese population on genes coding for proteins involved in the elimination of drugs currently used for the treatment of malaria and human immunodeficiency virus/acquired immunodeficiency syndrome. METHOD: The main polymorphisms on the cytochrome P450 (CYP) genes, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, and the multi-drug resistance 1 gene (MDR1) were genotyped in 78 healthy Vietnamese subjects. Pharmacokinetic metrics were available for CYP2A6 (coumarin), CYP2C19 (mephenytoin), CYP2D6 (metoprolol) and CYP3As (midazolam), allowing correlations with the determined genotype. RESULTS: In the CYP2 family, we detected alleles CYP2A6*4 (12%) and *5 (15%); CYP2B6*4 (8%), *6 (27%); CYP2C19*2 (31%) and *3 (6%); CYP2D6*4, *5, *10 (1, 8 and 44%, respectively). In the CYP3A family, CYP3A4*1B was detected at a low frequency (2%), whereas CYP3A5 *3 was detected at a frequency of 67%. The MDR1 3435T allele was present with a prevalence of 40%. Allele proportions in our cohort were compared with those reported for other Asian populations. CYP2C19 genotypes were associated to the S-4'-OH-mephenytoin/S-mephenytoin ratio quantified in plasma 4 h after intake of 100 mg mephenytoin. While CYP2D6 genotypes were partially reflected by the alpha-OH-metroprolol/metoprolol ratio in plasma 4 h after dosing, no correlation existed between midazolam plasma concentrations 4 h post-dose and CYP3A genotypes. CONCLUSIONS: The Vietnamese subjects of our study cohort presented allele prevalences in drug-metabolising enzymes that were generally comparable with those reported in other Asian populations. Deviations were found for CYP2A6*4 compared to a Chinese population (12 vs. 5%, respectively; P = 0.023), CYP2A6*5 compared with a Korean population (15 vs. <1%, respectively; P < 0.0001), a Malaysian population (1%; P < 0.0001) and a Chinese population (1%; P < 0.0001); CYP2B6*6 compared with a Korean population (27 vs. 12%; P = 0.002) and a Japanese population (16%; P = 0.021). Pharmacokinetic metrics versus genotype analysis reinforces the view that the predictive value of certain globally common variants (e.g. CYP2D6 single nucleotide polymorphisms) should be evaluated in a population-specific manner.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Aryl Hydrocarbon Hydroxylases
- genetics
- Asian Continental Ancestry Group
- genetics
- Cytochrome P-450 CYP2D6
- genetics
- Cytochrome P-450 CYP3A
- genetics
- Gene Frequency
- Genotype
- Humans
- Oxidoreductases
- N-Demethylating
- genetics
- P-Glycoprotein
- genetics
- Pharmacogenetics
- Polymorphism
- Genetic
- Vietnam
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Veiga, M I
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Asimus, Sara, 19 ...
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Ferreira, P E
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Martins, J P
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Cavaco, I
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Ribeiro, V
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Hai, T N
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Petzold, Max, 19 ...
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Björkman, A
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Ashton, Michael, ...
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Gil, J P
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