Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction
<p>Abstract</p> <p>Background</p> <p>Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-06-01
|
| Series: | Thrombosis Journal |
| Online Access: | http://www.thrombosisjournal.com/content/6/1/7 |
| _version_ | 1818141469394862080 |
|---|---|
| author | Seljeflot Ingebjørg Kierulf Peter Johansen Per Sjaatil Stine T Narum Sigrid Kringen Marianne K Sharikabad Mohammad N Haug Kari Arnesen Harald Brørs Odd |
| author_facet | Seljeflot Ingebjørg Kierulf Peter Johansen Per Sjaatil Stine T Narum Sigrid Kringen Marianne K Sharikabad Mohammad N Haug Kari Arnesen Harald Brørs Odd |
| author_sort | Seljeflot Ingebjørg |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA) alone.</p> <p>Aims</p> <p>The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR).</p> <p>Methods</p> <p>Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC) before PCR amplification (LightCycler) and melting point analysis.</p> <p>Results</p> <p>The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation.</p> <p>Conclusion</p> <p>CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.</p> |
| first_indexed | 2024-12-11T11:00:22Z |
| format | Article |
| id | doaj.art-1281f1aa6c9d46988cb61e236a800bb4 |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-12-11T11:00:22Z |
| publishDate | 2008-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-1281f1aa6c9d46988cb61e236a800bb42022-12-22T01:09:54ZengBMCThrombosis Journal1477-95602008-06-0161710.1186/1477-9560-6-7Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarctionSeljeflot IngebjørgKierulf PeterJohansen PerSjaatil Stine TNarum SigridKringen Marianne KSharikabad Mohammad NHaug KariArnesen HaraldBrørs Odd<p>Abstract</p> <p>Background</p> <p>Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA) alone.</p> <p>Aims</p> <p>The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR).</p> <p>Methods</p> <p>Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC) before PCR amplification (LightCycler) and melting point analysis.</p> <p>Results</p> <p>The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation.</p> <p>Conclusion</p> <p>CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.</p>http://www.thrombosisjournal.com/content/6/1/7 |
| spellingShingle | Seljeflot Ingebjørg Kierulf Peter Johansen Per Sjaatil Stine T Narum Sigrid Kringen Marianne K Sharikabad Mohammad N Haug Kari Arnesen Harald Brørs Odd Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction Thrombosis Journal |
| title | Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction |
| title_full | Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction |
| title_fullStr | Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction |
| title_full_unstemmed | Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction |
| title_short | Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction |
| title_sort | warfarin dose and inr related to genotypes of cyp2c9 and vkorc1 in patients with myocardial infarction |
| url | http://www.thrombosisjournal.com/content/6/1/7 |
| work_keys_str_mv | AT seljeflotingebjørg warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT kierulfpeter warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT johansenper warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT sjaatilstinet warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT narumsigrid warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT kringenmariannek warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT sharikabadmohammadn warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT haugkari warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT arnesenharald warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction AT brørsodd warfarindoseandinrrelatedtogenotypesofcyp2c9andvkorc1inpatientswithmyocardialinfarction |