Molecular Diagnosis & Therapy

, Volume 10, Issue 1, pp 29–40 | Cite as

Interethnic and Intraethnic Variability of CYP2C8 and CYP2C9 Polymorphisms in Healthy Individuals

  • Elena García-Martín
  • Carmen Martínez
  • José M. Ladero
  • José A. G. Agúndez


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.



Research at authors’ laboratories is financed by grants SAF 2003-00967 from Ministerio de Ciencia y Tecnología, FIS 02/0255 from Fondo de Investigatión Sanitaria, Instituto de Salud Carlos III, Madrid, Spain; SCSS0464 and SCSS0465 from Consejería de Sanidad y Consumo, Junta de Extremadura, Merida, Spain.

The authors have no conflicts of interest that are directly relevant to the content of this review.


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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Elena García-Martín
    • 1
  • Carmen Martínez
    • 2
  • José M. Ladero
    • 3
  • José A. G. Agúndez
    • 2
  1. 1.Department of Biochemistry & Molecular Biology, School of SciencesUniversity of ExtremaduraBadajozSpain
  2. 2.Department of Pharmacology, Medical SchoolUniversity of ExtremaduraBadajozSpain
  3. 3.Service of GastroenterologySan Carlos University Hospital, Complutense UniversityMadridSpain

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