The CYP2C19 Enzyme Polymorphism

Wedlund, Peter J.

doi:10.1159/000028398

Cited by 152 publications

(113 citation statements)

References 44 publications

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“…However, in contrast to the Asian population, the prevalence of PM of CYP2C19 in Caucasians is much lower, that is, about 2.8 versus 21.3%, respectively, in Caucasians and Japanese. 81 Schwab et al 82 could show significant differences considering the efficacy of lansoprazole-based quadruple therapy between Caucasian patients carrying wild-type alleles, one and two CYP2C19 defect alleles with cure rates of 80.2, 97.8 and 100% in the respective groups. The authors concluded that eradication rates of H. pylori highly depend on CYP2C19 genotype in white patients if the standard doses of lansoprazole are administered within this regimen and carriers of CYP2C19 wild-type allele might benefit from a higher PPIs dosage.…”

Section: Ulcer Disease and Proton Pump Inhibitorsmentioning

confidence: 99%

The clinical role of genetic polymorphisms in drug-metabolizing enzymes

et al. 2007

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Section: Ulcer Disease and Proton Pump Inhibitorsmentioning

confidence: 99%

The clinical role of genetic polymorphisms in drug-metabolizing enzymes

et al. 2007

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“…8 Recently it has been shown that CYP2C19 has a role in the activation of clopidogrel, an antiaggregant drug. SNP variants of this enzyme interfere with the clinical activity of this drug, to the point where the FDA were induced to request a modification in the prescribing information of the drug.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial

et al. 2010

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The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19*17 and two single-nucleotide polymorphisms for the gene SULT1A1 were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (P ¼ 0.035). In an exploratory analysis, among 58 women with a CYP2D6*2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (P ¼ 0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmacogenomics in tailoring tamoxifen treatment.

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“…More than 75 drugs are metabolized by CYP2D6, including antidepressants, selective serotonin reuptake inhibitors and opioids [2]. CYP2C19 metabolizes more than 25 drugs including proton pump inbibitors and some antidepressants [3]. Populations in different environments and with different genetic backgrounds show interethnic differences in drug metabolism [4].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population

Halling

Petersen

Damkier

et al. 2005

Eur J Clin Pharmacol

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Objective: The purpose of the study was to study the distribution of poor and extensive metabolizers of CYP2C19 and CYP2D6 and to genotype for CYP2C8 and CYP2C9 among 312 randomly selected Faroese. Methods and Results:The participants were phenotyped for CYP2D6 with the use of sparteine. The distribution of the sparteine metabolic ratio (sparteine/didehydrosparteines) was bimodal, and 14.5% (n=44) (95% CI 10.7-18.9%) of the subjects were phenotyped as poor metabolizers. The frequency of poor metabolizers was higher (P=0.0002; χ 2 test) among the Faroese than in other European populations (7.4%). Genotype analysis for the CYP2D6*3, *4, *6 and *9 alleles were performed using real-time PCR (TaqMan®), and we found 14.6% (n=45) (95% CI 10.8-19.0%) with deficient CYP2D6 genes (*3/*4, *4/*4, *4/*6, *6/*6) in the Faroese population.The subjects were phenotyped for CYP2C19 with the use of mephenytoin and 10 subjects, i.e. 3.2% (95% CI 1.6-5.9%) were phenotyped as poor metabolizers. Genotype analysis for the CYP2C19*2 and *3 alleles was performed by PCR analysis and 2.9% (n=9) (95% CI 1.3-5.4%) of the Faroese were found to have a deficient CYP2C19 gene all explained by the CYP2C19*2/*2 genotype. The allele frequencies of the CYP2C9*2 and CYP2C9*3 alleles were 8.8% (95% CI 6.7-11.4%) and 5.3% (95% CI 3.7-7.4%), respectively, while the CYP2C8*3 allele frequency was 6.9% (95% CI 5.0-9.2%). Real-time PCR (TaqMan®) was used for both CYP2C9 and CYP2C8 genotype analyses. Conclusion:The frequency of CYP2D6 poor metabolizers is two fold higher among the Faroese population compared to other Caucasians, while the frequencies of Faroese subjects with decreased CYP2C19, CYP2C8 and CYP2C9 enzyme activity are the same as seen in other Caucasian populations. A possible consequence might be a higher incidence of side effects among Faroese patients taking pharmaceuticals that are CYP2D6 substrates.

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The CYP2C19 Enzyme Polymorphism

Cited by 152 publications

References 44 publications

The clinical role of genetic polymorphisms in drug-metabolizing enzymes

The clinical role of genetic polymorphisms in drug-metabolizing enzymes

Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial

Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population

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