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Pharmacogenetics: promise or reality?

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RIMeL / IJLaM 2009; 5 (Suppl.)

Ricevuto: 20-07-2009 Pubblicato on-line: 11-09-2009

Corrispondence to: Dr. Ron H.N. van Schaik, Erasmus MC Rotterdam, The Netherlands. E-mail: [email protected]

Pharmacogenetics: promise or reality?

R.H.N. van Schaik

Erasmus MC Rotterdam, The Netherlands

A common problem in medicine is that there are differ- ences in how patients repond to drugs. Whereas most in- dividuals will tolerate the standard dosages well, certain patients may either experience severe toxicity on the same dose, or may eventually show to be subtherapeutically treat- ed. Since the 1960s, we are aware that individuals may differ in metabolizing capacity, due to genetic polymor- phisms encosing drug metabolizing enzymes.

Examples are NAT2 polymorphisms and isoniazide (used to treat tuberculosis), TPMT and azathioprine/6- mercaptopurine (Crohns disease, Acute Lymphatic Leuke- mia) and cytochrome P450 2D6 (CYP2D6). Yet, this knowl- edge has not resulted at that time in a large implementa-

tion for patient care. In the last 5 years, however, impor- tant improvements have been made, both in availability of genotyping techniques as in knowledge about translat- ing genotypes to phenotypes.

Interesting new applications are CYP2D6 testing for tamoxifen therapy (breast cancer), CYP2C9/VKORC1 analysis for anticoagulation, HLA-B5701 testing for abacav- ir (HIV treatment) and CYP2C19 analysis for clopidogrel (anticoagulation). Because of these examples, there seems to be a growing acceptance of pharmacogenetic testing.

How far are we at this moment? Can we integrate phar-

macogenetic testing already in routine diagnostics, or are

we still too early?

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