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- Veiga, M I, et al.
(author)
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Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam.
- 2009
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In: European journal of clinical pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 65:4, s. 355-63
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Journal article (peer-reviewed)abstract
- 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.
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- Ferreira, PE, et al.
(author)
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Pharmacogenetic tools for malaria and TB in the Developing World
- 2008
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In: Personalized medicine. - : Future Medicine Ltd. - 1744-828X .- 1741-0541. ; 5:6, s. 627-639
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Journal article (peer-reviewed)abstract
- Some of the largest therapeutic drug exposures in the planet involve drugs employed against malaria and TB, two main global infectious diseases. Amodiaquine for malaria and isoniazid for TB are two pivotal drugs in the management of these diseases. Both drugs have been associated with severe adverse events. Amodiaquine and isoniazid are metabolized polymorphically by CYP2C8 and N-acetyltransferase 2, respectively. The polymorphic genes coding for these enzymes presently represent the best candidates for the application of personal pharmacogenetics for these diseases. We review the main reasons for this view, while asking the pivotal question of whether it is presently possible for pharmacogenetic-based personalized medicine to be applied in the malaria and TB settings of the Developing World.
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