141Use of Pharmacogenetics in Clinical Pharmacology
Application of CYP2C19 Pharmacogenetics
Epigenomics and Personalized Medicine
CYP2C19 gene has ~2,000 reference SNPs containing 28 registered alleles in the
P450 Allele Nomenclature Committee and the number continues to increase.
However, biological functions of CYP2C19 SNPs is not fully understood. Functional
information on the variant is essential for justifying its clinical use. Mostly only
common variants (minor allele frequency >5 %) that represent CYP2C192, 3,
*17, and others have been studied. Discovery of new genetic variants is outstripping
the generation of knowledge on the biological meanings of existing variants.
Alternative strategies may be needed to fi ll this gap. A study has summarized up-to-
date knowledge on functional CYP2C19 variants discovered in phenotyped humans
studied at the molecular level in vitro (Lee et al. 2013 ). Understanding the func-
tional signifi cance of CYP2C19 variants is an essential step toward shifting the
current medical paradigm to highly personalized therapeutic regimens.
Genotyping for Identifying Responders to Sulfasalazine
One example of importance of pharmacogenetics in determining drug effi cacy is
that of sulfasalazine − an effective agent for chronic discoid lupus erythematosus
(CDLE) − where the response to treatment is varies considerably between patients
and is also unpredictable. The reason for this might relate to differences in metabo-
lism of the drug, which is extensively acetylated by the polymorphic enzyme
N-acetyltransferase 2 (NAT2). Genetic polymorphism of NAT2 is responsible for
differences in the response to sulfasalazine in patients with CDLE. Genotyping can
predict outcome of treatment according to whether the patients are slow acetylators
(SAs) or rapid acetylators (RAs); non-responders are SAs whereas RAs respond to
treatment with a complete or marked remission of the disease. In addition, SAs
seem to be more prone to toxic events. Therefore, candidates for sulfasalazine ther-
apy should be genotyped to identify those patients who might benefi t from the drug.
HLA Alleles Associated with Lumiracoxib-Related Liver Injury
Drug-induced liver injury is a rare but serious side effect seen in a subset of indi-
viduals taking certain drugs. Lumiracoxib (Novartis’ Prexige), a selective cycloox-
ygenase- 2 (COX-2) inhibitor developed for the symptomatic treatment of
osteoarthritis and acute pain, was withdrawn or not approved in most major drug
markets because of concerns over hepatotoxicity. A case-control genome-wide
Use of Pharmacogenetics in Clinical Pharmacology