Polymorphisms of human cytochrome P450 2C9 and the functional relevance

Zhou, Shu Feng; Zhou, Zhi Wei; Huang, Min

doi:10.1016/j.tox.2009.08.013

Cited by 103 publications

(85 citation statements)

References 322 publications

(217 reference statements)

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“…A relatively lower frequency of the mutant alleles of this gene (4%) has previously been reported in the north Indian population (30). The CYP2C9*2 variant is reported to be more frequent among Caucasian populations, with ~1% of the population being homozygous carriers while 22% are heterozygous; corresponding figures for the CYP2C9*3 allele are 0.4% and 15%, respectively (31). In contrast, only 6.5% of the population in the current study was heterozygous for the CYP2C9*2 variant and 11% was heterozygous for the *3 variant, and none of the population was homozygous for variant alleles.…”

Section: Discussioncontrasting

confidence: 68%

Genotyping of CYP2C9 and VKORC1 polymorphisms predicts south Indian patients with deep vein thrombosis as fast metabolizers of warfarin/acenocoumarin

Arunkumar

Vishnuprabu

Nupur

et al. 2017

DD&T

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Section: Discussioncontrasting

confidence: 68%

Genotyping of CYP2C9 and VKORC1 polymorphisms predicts south Indian patients with deep vein thrombosis as fast metabolizers of warfarin/acenocoumarin

Arunkumar

Vishnuprabu

Nupur

et al. 2017

DD&T

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“…However, in Asians, the same alleles are mostly absent or present at frequencies of not more than 3% [41,42]. A similar range in distribution of allelic frequencies is observed across the African continent, but with the noteworthy finding that populations in northern Africa appear to harbor CYP2C9*2 and *3 alleles at higher frequencies with a mean of 11.8%, whereas the mean allelic frequency in sub-Saharan Africa is 0.6% [8], similar to that in African-Americans [42,43]. This indicates clear inter-ethnic differences in the distribution of CYP2C9*2 and *3, as the populations in northern Africa are mostly of Afro-Asiatic origin, and the majority of those who reside in sub-Saharan Africa are of Bantu/Niger-Congo origin.…”

Section: Cyp2c9 and The Management Of Cardiovascular/circulatory Disementioning

confidence: 99%

“…In Caucasian populations, the frequency of these alleles ranges from 8% to over 20% [40]. However, in Asians, the same alleles are mostly absent or present at frequencies of not more than 3% [41,42]. A similar range in distribution of allelic frequencies is observed across the African continent, but with the noteworthy finding that populations in northern Africa appear to harbor CYP2C9*2 and *3 alleles at higher frequencies with a mean of 11.8%, whereas the mean allelic frequency in sub-Saharan Africa is 0.6% [8], similar to that in African-Americans [42,43].…”

Section: Cyp2c9 and The Management Of Cardiovascular/circulatory Disementioning

confidence: 99%

Priority pharmacogenetics for the African continent: focus on CYP450

Alessandrini

Pepper

2014

Pharmacogenomics

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SummaryCountries in Africa have a high burden of communicable disease, and are experiencing an increase in non-communicable diseases due to the effects of globalization, industrialization and urbanization.The costs incurred through adverse drug reactions and non-responsiveness to therapy further aggravate the situation, and the application of pharmacogenetic principles is likely to provide some relief. Having undertaken an extensive evaluation of CYP450 reports in Africa, our objective was to map out areas of need based on regional disease burdens. The data confirms a paucity of CYP450 reports and illustrates large regions for which no population information exists. There is a dire need to address the health problems of Africa, and wide-scale pharmacogenetic profiling of these populations will add significantly to improving patient care on the continent. Priority pharmacogenetics for the African continent gives precedence to the profiling of clinically relevant pharmacogenetic biomarkers, and defines the immediate need in the context of disease burden.

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“…CYP2C9 is one isoform of the cytochrome P450 complex and participates in the metabolism of ~15% of the clinically used drugs, including non-steroidal anti-inflammatory drugs, angiotensin II blockers and oral anticoagulants (22). CYP2C9 is located on chromosome 10q24.2, and its alleles have been identified.…”

Section: Discussionmentioning

confidence: 99%

Clinical application of a new warfarin-dosing regimen based on the CYP2C9 and VKORC1 genotypes in atrial fibrillation patients

Jiang

Xian

et al. 2016

Biomedical Reports

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Abstract. The polymorphisms of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) are important genetic factors for warfarin dose determinations. The present study aimed to investigate the contribution of the CYP2C9 and VKORC1 genotypes to warfarin dose requirement in atrial fibrillation (AF) patients, and to evaluate the clinical application of a warfarin-dosing algorithm. A total of 122 AF patients with a target international normalized ratio of 2.0 to 3.0 were included to determine the genotypes of CYP2C9 (rs1057910) and VKORC1 (rs9923231). A warfarin-dosing algorithm was developed based on age, height, and the CYP2C9 and VKORC1 genotypes of AF patients. The results indicated that the mean warfarin daily dose requirement was lower in the CYP2C9 * 1/ * 3 genotype compared with those in the homozygous wild-type CYP2C9 * 1/ * 1 patients (P<0.05), and was higher in patients with the VKORC1 AG and GG genotypes compared with those with the AA genotype (P<0.05). The multivariate regression model showed that age, height, and the CYP2C9 and VKORC1 genotypes were the best variables for estimating warfarin dose (R 2 =56.4%). A new warfarin-dosing algorithm was developed and its validity was confirmed in a second cohort of AF patients. During the 50-day follow-up, 63.3% (19/30) of control group patients and 86.7% (26/30) of patients in the experimental group acquired the warfarin maintenance dose. Among all the patients who acquired the warfarin maintenance dose, the mean time elapse from initiation until warfarin maintenance dose was significantly less in the experimental group (25.8±1.7 day) compared to the control group (33.1±1.9 day) (P<0.05). There was significant linear correlation between predicted warfarin maintenance dose and actual dose (r=0.822, P<0.01). In conclusion, a new warfarin-dosing algorithm was developed based on the CYP2C9 and VKORC1 genotypes, and it can shorten the time elapse from initiation until warfarin maintenance dose in AF patients with warfarin therapy.

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Polymorphisms of human cytochrome P450 2C9 and the functional relevance

Cited by 103 publications

References 322 publications

Genotyping of <i>CYP2C9</i> and <i>VKORC1</i> polymorphisms predicts south Indian patients with deep vein thrombosis as fast metabolizers of warfarin/acenocoumarin

Genotyping of <i>CYP2C9</i> and <i>VKORC1</i> polymorphisms predicts south Indian patients with deep vein thrombosis as fast metabolizers of warfarin/acenocoumarin

Priority pharmacogenetics for the African continent: focus on CYP450

Clinical application of a new warfarin-dosing regimen based on the CYP2C9 and VKORC1 genotypes in atrial fibrillation patients

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