[Clinical pharmacogenomics for CYP2C8 and CYP2C9: general concepts and application to the use of NSAIDs].
OBJECTIVE
To study the major mutations in genes CYP2C8 and CYP2C9, their frequency in populations of diverse ethnical descent, their analysis methods, and the major drugs with affected metabolism, with a special emphasis on NSAIDs.


METHODS
Repeated searches of Pubmed (January 1966-January 2006) and Scholar Google were performed. All searches were restricted to studies in humans, and papers not written in Spanish or English were excluded.


RESULTS
Ten allelic variants of CYP2C8 and 24 of CYP2C have been reported. Not all of them exert a relevant effect on drug metabolism. In Caucasians 22% of CYP2C8 genes and 31% of CYP2C9 genes have mutations. In Asians fewer than 1% and nearly 3% are mutated, respectively. Major identification methods include endonuclease digestion, PCR, pyrosequencing, and microarrays. Not all NSAIDs are exclusive substrates for CYP2C8/9. The usefulness of allelic variant analysis varies with each individual drug. The risk for digestive hemorrhage associated with the CYP2C9 genotype is particularly relevant when using aceclofenac, celecoxib, diclofenac, ibuprofen, indomethacin, lornoxicam, piroxicam, or naproxen.


CONCLUSIONS
Although CYP2C8/9 activity plays an essential role in the metabolism of and clinical response to many NSAIDs, the use of pharmacogenomic techniques is not equally useful for all these drugs.
Martínez
C
C
Departamento de Farmacología, Facultad de Medicina, Universidad de Extremadura, Servicio de Cirugía General, Hospital Universitario Infanta Cristina, Badajoz.
Blanco
G
G
García-Martín
E
E
Agúndez
J A G
JA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D009154:Mutation
D000894:Anti-Inflammatory Agents, Non-Steroidal; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8