Important Haplotype Information for CYP2C9
Submitted by: Derek Van Booven (CREATE), Michelle Whirl Carrillo (PharmGKB)
Reviewed by: Reviewed
Submitted date: January 16th, 2007
There are Two Important Haplotypes for CYP2C9.
- CYP2C9*2:
- CYP2C9*3:
CYP2C9*2
| Gene HGNC Name: | CYP2C9 |
|---|---|
| Haplotype Significance: | CYP2C9*2 is defined by the 144Arg>Cys SNP. Variant frequencies are 10-20% for Caucasian populations while considerably less in the African (0-6%) and Asian (1-3%) populations. The variant was first described by Rettie et al [8004131] as having impaired the ability to metabolize warfarin. It is also thought to alter the interaction with NADPH cytochrome P450 oxidoreductase [9241660]. |
| Does this haplotype span more than one gene? | Unknown |
| Definitive Publication or Website: | http://www.imm.ki.se/CYPalleles |
| Drugs: | NSAIDs (16118328), COX-2 inhibitors (12893985), tolbutamide (15637526), glipizide (15637526), fluvastatin (15637526), warfarin (8004131), phenytoin (11434505) |
| Phenotypes/Diseases: | N/A |
| Phenotype Data Sets: | WUSTL warfarin dosing data, group A, Hot flashes in tamoxifen patients, CYP2C9 variants and flurbiprofen metabolism, CYP2C9 variants and naproxen metabolism, CYP2C9 variants and piroxicam metabolism, Effects of dapsone on CYP2C9 variants and flurbiprofen metabolism, Effects of dapsone on CYP2C9 variants and naproxen metabolism, Lipid measurement in tamoxifen study-set 2, Meperidine N-demethylation by human CYP450 isoforms, Patient responses to tamoxifen, Thyroid binding globulin in tamoxifen patients |
| Key Haplotypes: | CYP2C9*2 |
| Key PubMed IDs: | 9241660, 8004131 |
| How many SNPs, indels, repeats define this haplotype? | CYP2C9 144Arg>Cys |
CYP2C9*3
| Gene HGNC Name: | CYP2C9 |
|---|---|
| Haplotype Significance: | CYP2C9*3 is defined by the 359Ile>Leu SNP. Variant frequencies are less than 10% for every population and extremely rare in African populations. The low activity from *3 appears to be the result of decreased capacity to metabolize substrate (reduced Vmax, increased Km). The *3 variant has been shown to be associated with low warfarin dose requirement and risk for bleeding complications [10073515]. |
| Does this haplotype span more than one gene? | Unknown |
| Definitive Publication or Website: | http://www.imm.ki.se/CYPalleles |
| Drugs: | NSAIDs (16118328), COX-2 inhibitors (12893985), tolbutamide (15637526), glipizide (15637526), fluvastatin (15637526) , warfarin (8004131), phenytoin (11434505) |
| Phenotypes/Diseases: | N/A |
| Phenotype Data Sets: | WUSTL warfarin dosing data, group A, Hot flashes in tamoxifen patients, CYP2C9 variants and flurbiprofen metabolism, CYP2C9 variants and naproxen metabolism, CYP2C9 variants and piroxicam metabolism, Effects of dapsone on CYP2C9 variants and flurbiprofen metabolism, Effects of dapsone on CYP2C9 variants and naproxen metabolism, Lipid measurement in tamoxifen study-set 2, Meperidine N-demethylation by human CYP450 isoforms, Patient responses to tamoxifen, Thyroid binding globulin in tamoxifen patients |
| Key Haplotypes: | CYP2C9*3 |
| Key PubMed IDs: | 10073515, 8873220 |
| How many SNPs, indels, repeats define this haplotype? | CYP2C9 359Ile>Leu |