Important Haplotype Information for VKORC1
Submitted by: Ryan Owen
Reviewed by: Under Review
Submitted date: January 29th, 2007
There are Four Important Haplotypes for VKORC1.
- VKORC1*1
- VKORC1*2
- VKORC1*3
- VKORC1*4
1. VKORC1*1
| Gene HGNC Name: | VKORC1 |
|---|---|
| Haplotype Name | VKORC1*1 |
| Does this haplotype span more than one gene? |
Unknown |
| What is the definitive publication or website defining this haplotype? |
VKORC1 haplotypes and their impact on the inter-individual and inter-ethnic variability of oral anticoagulation. Geisen et al [PMID: 16270629]. |
| Haplotype Summary: | This haplotype is the same as the reference sequence AY587020, and is considered to be the ancestral haplotype of VKORC1 [16270629]. VKORC1*1 seems to only occur at high frequencies in populations of African origin, but VKORC1*1 is not the most common haplotype in the African population reported by Geisen et al [16270629]. |
| Key PubMed IDs: | 16270629 |
| How many SNPs, indels, or repeats define this haplotype? |
The reference sequence: AY587020 |
| Linked to Variant Worksheets? |
No |
| Drugs/Substrates: | Warfarin, coumarin, acenocoumarol |
| Key Phenotypes/Diseases: | Atrial Fibrillation, Coagulation Protein Disorders, Hemorrhage, Vascular Diseases |
| Phenotype Datasets |
WUSTL warfarin doing data, group A |
2. VKORC1*2
| Gene HGNC Name: | VKORC1 |
|---|---|
| Haplotype Name | VKORC1*2, H1 and H2, Haplotype group A |
| Does this haplotype span more than one gene? | Unknown |
| What is the definitive publication or website defining this haplotype? | VKORC1 haplotypes and their impact on the inter-individual and inter-ethnic variability of oral anticoagulation. Geisen et al [PMID: 16270629]. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. Reider et al [PMID: 15930419]. |
| Haplotype Summary: | VKORC1*2, or H1 and H2, or haplotype group A of VKORC1 all represent the haplotype that is associated with response to a lower dose of warfarin. There are subtle differences in the definitions of these haplotypes, but all contain an A allele at position 3673 and a T allele at position 6484 of AY587020. VKORC1*2 was defined by Geisen et al [16270629], and H1 and H2 (haplotype group A) were defined by Reider et al [15930419]. VKORC1*2 is the predominant haplotype in the Asian population, and it is also quite common among Caucasians. This haplotype also exists in African populations, but it is less frequent [16270629]. |
| Key PubMed IDs: | 15930419 16270629 |
| How many SNPs, indels, or repeats define this haplotype? | VKORC1*2 (4), H1 (5), H2 (6), haplotype group A includes both H1 and H2. |
| Linked to Variant Worksheets? | G3673A, C6484T |
| Drugs/Substrates: | Warfarin, coumarin, acenocoumarol |
| Key Phenotypes/Diseases: | Atrial Fibrillation, Coagulation Protein Disorders, Hemorrhage, Vascular Diseases |
| Phenotype Datasets: | WUSTL warfarin dosing data, group A |
3. VKORC1*3
| Gene HGNC Name: | VKORC1 |
|---|---|
| Haplotype Name | VKORC1*3 |
| Does this haplotype span more than one gene? | Unknown |
| What is the definitive publication or website defining this haplotype? | VKORC1 haplotypes and their impact on the inter-individual and inter-ethnic variability of oral anticoagulation. Geisen et al [PMID: 16270629]. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. Reider et al [PMID: 15930419]. |
| Haplotype Summary: | Most of the VKORC1 haplotype literature uses either the terminology of Reider et al [15930419] or Geisen et al [16270629] when describing VKORC1 haplotypes, but this can get confusing when attempting to delineate between VKORC1*3 and VKORC1*4. In the analysis of Reider et al, both VKORC1*3 and VKORC1*4 are included in haplotype group B. Again, although there are subtle differences, the H7 and H8 groups of Reider approximately correspond to the VKORC1*3 group of Geisen et al, whereas H9 of Reider (also in haplotype group B) corresponds more closely with VKORC1*4 as defined by Geisen. The key SNP for the differentiating between VKORC1*3 and VKORC1*4 is the allele at position 9041 [16270629]. D'Andrea et al found a trend towards increased warfarin dose requirements for patients homozygous for the A allele at position 9041 versus patients who were either heterozygous or homozygous for the G allele [15358623], and Herman et al also found that the allele at position 9041 influenced warfarin dosing requirements 16676068. VKORC1*3 is the most common haplotype in the African population, and is also very common among Caucasians (similar to the frequency of VKORC1*2 in Caucasian populations). |
| Key PubMed IDs: | 15930419 16270629 15358623 16676068 |
| How many SNPs, indels, or repeats define this haplotype? |
VKORC1*3 (1), H7 (1), H8 (2), haplotype group B contains H7, H8, and H9 |
| Linked to Variant Worksheets? | G9041A |
| Drugs/Substrates: | Warfarin, coumarin, acenocoumarol |
| Phenotypes/Diseases: | Atrial Fibrillation, Coagulation Protein Disorders, Hemorrhage, Vascular Diseases |
| Phenotype Datasets: | WUSTL warfarin dosing data, group A |
4. VKORC1*4
| Gene HGNC Name: | VKORC1 |
|---|---|
| Haplotype Name | VKORC1*4 |
| Does this haplotype span more than one gene? | Unknown |
| What is the definitive publication or website defining this haplotype? | VKORC1 haplotypes and their impact on the inter-individual and inter-ethnic variability of oral anticoagulation. Geisen et al [PMID: 16270629]. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. Reider et al [PMID: 15930419] |
| Haplotype Summary: | VKORC1*4 is similar to VKORC1*3 but it contains the reference allele at position 9041 [16270629]. In the analysis of Rieder et al, VKORC1*4 was included in haplotype group B, and thus was associated with a higher dose of warfarin [15930419 16676068]. However, some groups have shown that the allele at position 9041 may itself be predictive of a high warfarin dose phenotype [15358623 16676068], and this would potentially distinguish VKORC1*3 from VKORC1*4 as the "high dose" haplotype. |
| Key PubMed IDs: | 16270629 15930419 16676068 15358623 |
| How many SNPs, indels, or repeats define this haplotype? | VKORC1*4 (1), H9 (3), haplotype group B contains H7, H8, and H9 |
| Linked to Variant Worksheets? | No |
| Drugs/Substrates: | Warfarin, coumarin, acenocoumarol |
| Phenotypes/Diseases: | Atrial Fibrillation, Coagulation Protein Disorders, Hemorrhage, Vascular Diseases |
| Phenotype Datasets: |
WUSTL warfarin dosing data, group A |