The first (and one of the more important) gene involved in pharmacogenomic studies is CYP2D6. It is believed that the enzyme encoded by this gene (cytochrome P450-2D6) is involved in the metabolism of about 25% of drugs available today. So far, more than 100 CYP2D6 alleles have been reported to be of pharmacogenomic relevance. In the last years CYP2D6 genotyping has been elaborated to classify patients into four metabolizer phenotypes: ultrarapid, extensive, intermediate and poor.
Many other cytochrome P450 genes like CYP2C9 and CYP2C19 have been pharmacogenetically characterized. CYP2C9 alleles, along with VKORC1 and CYP4F2 alleles, are important in warfarin efficacy and dosing. The CYP2C19*2 allele has been associated with a lower production of active metabolites of clopidrogel, higher platelet aggregation ratio and adverse clinical outcome. Other notable associations of these two genes are with phenytoin, acenocoumarol, glibenclamide, gliclazide, glimepiride, phenprocoumon, and tolbutamide (CYP2C9) and with carisoprodol, citalopram, clobazam, clopidogrel, dexlansoprazole, diazepam, esomeprazole, lansoprazole, nelfinavir, omeprazole, pantoprazole, prasugrel, rabeprazole, drospirenone ethinyl estradiol, atazanavir, axitinib, ticagrelor and voriconazole (CYP2C19).
Other important pharmacogenomic markers have been identified in the following gene/drug associations: ABCB1/aliskiren, CYP2B6/efavirenz, CYP34A/ticagrelor, aripiprazole, cabazitaxel, darunavir, dronedarone, fosamprenavir, gefitinib, indinavir, ivabradine, nelfinavir, posaconazole, ritonavir, ruxolitinib, sirolimus, sunitinib, telithromycin, tipranavir, voriconazole, zonisamide, CYP3A5/tacrolimus, DPYD/tegafur, capecitabine, fluorouracil, NAT2/isosorbide dinitrate and hydralazine hydrochloride, rifampin-isoniazid-pyrazinamid, SLC22A2/fampridine, SLCO1B1/simvastatin, TPMT/azathioprine, mercaptopurine, thioguanine, azathioprine, UGT1A1/irinotecan, IFNL3/PEG-interpheron-α (PEG-IFN alpha).
A working group of experts from the academy and the industry has actually collected the information on the most important genes so far recognized to be of relevance for their pharmacogenomic correlation. This is the PharmaADME working group, whose list have been used also to design commercial kits for genetic testing (the ADME gene list).
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