Drug Metabolism

The general topic of pharmacogenomics includes the study of how SNPs alter the efficacy or safety of drugs. For FDA-approved drugs, there are published dosing guidelines based on genotypes; a list primarily published by the CPIC (Clinical Pharmacogenetics Implementation Consortium) that is maintained and curated by PharmGKB is available here.

Within the body, the liver is the primary organ responsible for metabolizing (i.e. breaking down and thereby helping to absorb) most things you ingest. Within it, the proteins known as the cytochrome p450's have the primary role, and so SNPs in the genes encoding this family of proteins play a major role in drug metabolism.

There are over 60 cytochrome ("cyp") p450 genes in the human genome, classified into 14 different subfamilies. However, most of the commonly prescribed and over-the-counter drugs are metabolized by one (or in some cases, more) of the following p450's:

Home Page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee

Updated List of Cytochrome P450 Drug Interactions Here

Cytochrome p450 SNPs cited as clinically important in metabolizing ~50% of the 200 most prescribed drugs (by Rx count) in the US, including, in particular, NSAIDs metabolized mainly by CYP2C9, proton-pump inhibitors metabolized by CYP2C19, and beta blockers, antipsychotics and antidepressants metabolized by CYP2D6 [PMID 18695978]: rs2069514 rs762551 rs2279343 rs3745274 rs22799343 rs28399499 rs11572103 rs11572080 rs10509681 rs1799852 rs1057910 rs4244285 rs4986893 rs12248560 rs35742686 rs3892097 rs5030655 rs1065852 rs28371706 rs16947 rs28371725 rs2740574 rs776746

according to Dr Steve Murphy the site GeneMedRx is used by doctors to flag drug warnings. A number of the genotypes of interest are covered by genosets. Listing them here will help group them in promethease reports.

1A2 Diminished induction
1A2 Normal induction
1A2 Hyperinduction
gs153 2C19 Ultra-rapid metabolizer
gs152 2C19 Poor metabolizer
gs151 2C19 Intermediate metabolizer
gs150 2C19 Normal metabolizer
gs126 2C9 Poor metabolizer
gs127 2C9 Intermediate metabolizer
2C9 Normal metabolizer
2D6 Poor metabolizer
2D6 Intermediate metabolizer
2D6 Normal metabolizer
2D6 Ultra Rapid Metabolizer
gs163 gs163-gs182 cover individual allels of CYP2D6
gs164
gs165
gs166
gs167
gs168
gs169
gs170
gs171
gs172
gs173
gs174
gs175
gs176
gs177
gs178
gs179
gs180
gs181
gs182
5HTT Heterozygous S/L
5HTT Homozygous Short S/S
5HTT Homozygous Long L/L
DPD Poor Metabolizer
DPD Intermediate Metabolizer
DPD Normal Metabolizer
HER2/Neu Positive
HER2/Neu Negative
rs2395029 HLA-B*5701 Positive
rs1801133 MTHFR C677T TT Poor Metabolizer
MTHFR C677T CC Normal Metabolizer
MTHFR C677T CT Intermediate Metabolize
gs140 NAT2 Slow acetylator
gs139 NAT2 Intermediate acetylator
gs138 NAT2 Rapid acetylator gs125 older
TPMT Poor metabolizer
TPMT Intermediate metabolizer
TPMT Normal metabolizer
UGT1A1 Normal metabolizer
UGT1A1 Intermediate metabolizer
UGT1A1 Poor metabolizer
VKORC 1639 AA Homozygous
VKORC 1639 GG Homozygous
VKORC 1639 GA Heterozygous