Markers / Condition
Which genes affect how medicines work for you?
Pharmacogenomics is the part of consumer genetics with the clearest clinical footing. Prescribing guidelines exist, written by the Clinical Pharmacogenetics Implementation Consortium, and several of these variants change what a doctor would choose or what dose they would start at. It is also the part most worth taking to an actual prescriber rather than acting on.
The markers
| Marker | Gene | What it does | Evidence |
|---|---|---|---|
| rs4244285 | CYP2C19 | CYP2C19 *2, loss of function | established |
| rs12248560 | CYP2C19 | CYP2C19 *17, increased function | established |
| rs1799853 | CYP2C9 | CYP2C9 *2 | established |
| rs1057910 | CYP2C9 | CYP2C9 *3 | established |
| rs9923231 | VKORC1 | Warfarin sensitivity, VKORC1 | established |
| rs2108622 | CYP4F2 | CYP4F2 and warfarin dose | established |
| rs4149056 | SLCO1B1 | Statin muscle side effects | established |
| rs2231142 | ABCG2 | ABCG2, statin response and uric acid | established |
| rs3892097 | CYP2D6 | CYP2D6 *4, the most common non-working version | established |
| rs1065852 | CYP2D6 | CYP2D6 *10, reduced function | established |
| rs776746 | CYP3A5 | CYP3A5 and tacrolimus dosing | established |
| rs1142345 | TPMT | Thiopurine sensitivity, TPMT *3C | established |
| rs116855232 | NUDT15 | Thiopurine sensitivity, NUDT15 | established |
| rs2395029 | HCP5 | Abacavir hypersensitivity marker | established |
| rs12979860 | IFNL4 | Interferon response in hepatitis C | established |
| rs1050828 | G6PD | G6PD deficiency, the A- variant | established |
| rs1799930 | NAT2 | Fast or slow acetylator | established |
CYP2C19 *2, loss of function
rs4244285 · CYP2C19
CYP2C19 activates clopidogrel, a very widely used antiplatelet drug, and clears several antidepressants and stomach-acid drugs. The *2 version does not work at all.
Two copies: Two *2 copies
CYP2C19 *17, increased function
rs12248560 · CYP2C19
The opposite variant: a promoter change that makes more enzyme than usual.
Two copies: Two *17 copies
CYP2C9 *2
rs1799853 · CYP2C9
CYP2C9 clears warfarin, phenytoin and most anti-inflammatory painkillers. The *2 version works at reduced capacity.
Two copies: Two *2 copies
CYP2C9 *3
rs1057910 · CYP2C9
The more severe of the two common CYP2C9 variants, with a larger effect on warfarin dose than *2.
Two copies: Two *3 copies
Warfarin sensitivity, VKORC1
rs9923231 · VKORC1
VKORC1 is warfarin's actual target. This promoter variant lowers how much of the target is made, so less warfarin is needed. Together with CYP2C9 it explains a large part of why the required dose varies so widely between people.
Two copies: High sensitivity
CYP4F2 and warfarin dose
rs2108622 · CYP4F2
The third gene in the standard warfarin dosing algorithm, after CYP2C9 and VKORC1. It affects vitamin K turnover, so carriers need slightly more warfarin.
Two copies: Two copies, so around ten per cent more warfarin is typically needed
Statin muscle side effects
rs4149056 · SLCO1B1
SLCO1B1 is the transporter that pulls statins out of the blood and into the liver, where they work. A reduced-function version leaves more statin circulating in muscle, which is where the aching comes from.
Two copies: Poor function
ABCG2, statin response and uric acid
rs2231142 · ABCG2
ABCG2 is a transporter that pumps drugs and waste out of cells. This reduced-function change raises blood levels of rosuvastatin and is also one of the strongest common genetic causes of raised uric acid and gout.
Two copies: Poor function
CYP2D6 *4, the most common non-working version
rs3892097 · CYP2D6
CYP2D6 handles roughly a quarter of all prescribed drugs, including codeine, tramadol, tamoxifen and many antidepressants. The *4 version does not work at all and is the most common cause of poor metabolism in European populations.
Two copies: Two *4 copies
CYP2D6 *10, reduced function
rs1065852 · CYP2D6
A reduced-function CYP2D6 version that is uncommon in Europe and carried by roughly half of people of East Asian descent, where it is the main cause of reduced CYP2D6 activity.
Two copies: Two reduced-function copies
CYP3A5 and tacrolimus dosing
rs776746 · CYP3A5
CYP3A5 clears tacrolimus, the main anti-rejection drug after organ transplant. Most Europeans carry two non-working copies and are non-expressors; most people of African descent express it and need substantially higher doses.
Two copies: Non-expressor
Thiopurine sensitivity, TPMT *3C
rs1142345 · TPMT
The other route to thiopurine toxicity, and the main one in European populations.
Two copies: Two reduced-function copies
Thiopurine sensitivity, NUDT15
rs116855232 · NUDT15
Azathioprine and mercaptopurine are used in inflammatory bowel disease, transplant medicine and leukaemia. NUDT15 variants cause severe bone-marrow suppression at normal doses, and they are the main cause of this in East Asian populations, where TPMT testing alone misses it.
Two copies: Poor metaboliser
Abacavir hypersensitivity marker
rs2395029 · HCP5
Abacavir, an HIV medicine, causes a dangerous hypersensitivity reaction in people carrying HLA-B*57:01. Testing before prescribing is mandatory, and it is one of the clearest successes in the whole field.
Two copies: Tag detected, two copies
Interferon response in hepatitis C
rs12979860 · IFNL4
This position predicted who would clear hepatitis C on interferon therapy better than any clinical factor. It is included partly as history: modern direct-acting antivirals cure almost everyone regardless of genotype, which is what real progress looks like.
Two copies: Less favourable genotype
G6PD deficiency, the A- variant
rs1050828 · G6PD
G6PD deficiency is the most common enzyme deficiency in the world. It is usually silent until something triggers it: certain antimalarials, some antibiotics, the gout drug rasburicase, and fava beans can all cause red blood cells to break down. The gene is on the X chromosome, so men have only one copy.
Two copies: Two copies, or hemizygous
Fast or slow acetylator
rs1799930 · NAT2
NAT2 clears a specific class of chemicals: several drugs, and the compounds formed when meat is charred. Roughly half of Europeans are slow acetylators and clear them sluggishly. The frequency shifted as populations took up farming, and it is one of the best documented cases of diet reshaping a detoxification gene.
Two copies: Slow acetylator at this position
Which versions do you carry?
All of these are readable from an ordinary home DNA test file, in your browser, without uploading it anywhere.
Read my fileCommon questions
Which genes affect how medicines work for you?
Pharmacogenomics is the part of consumer genetics with the clearest clinical footing. Prescribing guidelines exist, written by the Clinical Pharmacogenetics Implementation Consortium, and several of these variants change what a doctor would choose or what dose they would start at. It is also the part most worth taking to an actual prescriber rather than acting on. The markers most often cited are rs4244285 in CYP2C19, rs12248560 in CYP2C19, rs1799853 in CYP2C9, rs1057910 in CYP2C9, rs9923231 in VKORC1.
What does rs4244285 do?
CYP2C19 activates clopidogrel, a very widely used antiplatelet drug, and clears several antidepressants and stomach-acid drugs. The *2 version does not work at all. Carrying two copies: two *2 copies.
What does rs12248560 do?
The opposite variant: a promoter change that makes more enzyme than usual. Carrying two copies: two *17 copies.
What does rs1799853 do?
CYP2C9 clears warfarin, phenytoin and most anti-inflammatory painkillers. The *2 version works at reduced capacity. Carrying two copies: two *2 copies.
What does rs1057910 do?
The more severe of the two common CYP2C9 variants, with a larger effect on warfarin dose than *2. Carrying two copies: two *3 copies.
Reference information, not medical advice and not a diagnosis. See the medical disclaimer.