| Title |
Interethnic and Intraethnic Variability of CYP2C8 and CYP2C9 Polymorphisms in Healthy Individuals
|
|---|---|
| Published in |
Molecular Diagnosis & Therapy, August 2012
|
| DOI | 10.1007/bf03256440 |
| Pubmed ID | |
| Authors |
Elena García-Martín, Carmen Martínez, José M. Ladero, José A. G. Agúndez |
| Abstract |
Cytochrome P450 (CYP) superfamily members CYP2C8 and CYP2C9 are polymorphically expressed enzymes that are involved in the metabolic inactivation of several drugs, including, among others, antiepileptics, NSAIDs, oral hypoglycemics, and anticoagulants. Many of these drugs have a narrow therapeutic index, and growing evidence indicates a prominent role of CYP2C8 and CYP2C9 polymorphisms in the therapeutic efficacy and in the development of adverse effects among patients treated with drugs that are CYP2C8 or CYP2C9 substrates. In this review, we summarize present knowledge on human variability in the frequency of variant CYP2C8 and CYP2C9 alleles. Besides an expected interethnic variability in allele frequencies, a large intraethnic variability exists. Among Asian subjects, for example, statistically significant differences (p < 0.0001) in CYP2C9*3 allele frequencies between Chinese and Japanese individuals have been reported. In addition, individuals from East Asia present different allele frequencies for CYP2C9*2 and CYP2C9*3 compared with South Asian subjects (p < 0.0001). Among Caucasian Europeans, statistically significant differences for the frequency of CYP2C8*3, CYP2C9*2, and CYP2C9*3 exist (p < 0.0001). This indicates that Asian individuals or Caucasian European individuals cannot be considered as homogeneous groups regarding CYP2C8 or CYP2C9 allele frequencies. Caucasian American subjects also show a large variability in allele frequencies, which is likely to be related to ethnic ancestry. A higher frequency of variant CYP2C8 and CYP2C9 alleles is expected among Caucasian Americans with South European ancestry than in individuals with North European ancestry. The findings summarized in this review suggest that among individuals with Asian or European ancestry, intraethnic differences in the risk of developing adverse effects with drugs that are CYP2C8 or CYP2C9 substrates are to be expected. In addition, the observed intraethnic variability reinforces the need for proper selection of control subjects and points against the use of surrogate control groups for studies involving association of CYP2C8 or CYP2C9 alleles with adverse drug reactions or spontaneous diseases. |
Mendeley readers
The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Colombia | 1 | 2% |
| South Africa | 1 | 2% |
| Unknown | 58 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 12 | 20% |
| Researcher | 9 | 15% |
| Student > Ph. D. Student | 8 | 13% |
| Student > Master | 7 | 12% |
| Other | 4 | 7% |
| Other | 9 | 15% |
| Unknown | 11 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 20% |
| Pharmacology, Toxicology and Pharmaceutical Science | 11 | 18% |
| Biochemistry, Genetics and Molecular Biology | 10 | 17% |
| Agricultural and Biological Sciences | 9 | 15% |
| Chemistry | 5 | 8% |
| Other | 2 | 3% |
| Unknown | 11 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 March 2008.
All research outputs
#7,453,479
of 22,786,691 outputs
Outputs from Molecular Diagnosis & Therapy
#100
of 378 outputs
Outputs of similar age
#55,740
of 169,292 outputs
Outputs of similar age from Molecular Diagnosis & Therapy
#19
of 54 outputs
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