Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients
Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Mazandaran University of Medical Sciences and Health Services
2016-11-01
|
| Series: | Research in Molecular Medicine |
| Subjects: | |
| Online Access: | http://rmm.mazums.ac.ir/browse.php?a_code=A-10-26-31&slc_lang=en&sid=1 |
| _version_ | 1818275840859832320 |
|---|---|
| author | Reyhaneh Kameli Mandana Hasanzad Zahra Tahmasebi Fard Mojgan Babanejad Mahdieh Imeni Lotfollah Feizi Barnaji Atoosa Madadkar Seyed Hamid Jamaldini |
| author_facet | Reyhaneh Kameli Mandana Hasanzad Zahra Tahmasebi Fard Mojgan Babanejad Mahdieh Imeni Lotfollah Feizi Barnaji Atoosa Madadkar Seyed Hamid Jamaldini |
| author_sort | Reyhaneh Kameli |
| collection | DOAJ |
| description | Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on Iranian patients under warfarin treatment.
Materials and Methods: This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P<0.05 was considered as significance level.
Results: The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with ≥1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (–1639) GG genotype was significantly higher than GA and AA patients.
Conclusion: CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose; furthermore, the daily warfarin dose was not influenced by age, height, weight and sex. |
| first_indexed | 2024-12-12T22:36:09Z |
| format | Article |
| id | doaj.art-1ee80feb357846efa2c120fa05277d4d |
| institution | Directory Open Access Journal |
| issn | 2322-1348 2322-133X |
| language | English |
| last_indexed | 2024-12-12T22:36:09Z |
| publishDate | 2016-11-01 |
| publisher | Mazandaran University of Medical Sciences and Health Services |
| record_format | Article |
| series | Research in Molecular Medicine |
| spelling | doaj.art-1ee80feb357846efa2c120fa05277d4d2022-12-22T00:09:28ZengMazandaran University of Medical Sciences and Health ServicesResearch in Molecular Medicine2322-13482322-133X2016-11-01443844Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian PatientsReyhaneh Kameli0Mandana Hasanzad1Zahra Tahmasebi Fard2Mojgan Babanejad3Mahdieh Imeni4Lotfollah Feizi Barnaji5Atoosa Madadkar6Seyed Hamid Jamaldini7 Biology Department, Islamic Azad University of pharmaceutical sciences, Tehran, Iran Medical Sciences Research Center, Tehran Medical Branch, Islamic Azad University, Tehran, Iran Department of biology, Roudehen Branch, Islamic Azad University, Roudehen, Iran Cardiogenetics Research Center, Shahid Rajaie Cardiovascular Medical & Research Center, Tehran, Iran Biology Department, Islamic Azad University of pharmaceutical sciences, Tehran, Iran Cardiogenetics Research Center, Shahid Rajaie Cardiovascular Medical & Research Center, Tehran, Iran Cardiogenetics Research Center, Shahid Rajaie Cardiovascular Medical & Research Center, Tehran, Iran Cardiogenetics Research Center, Shahid Rajaie Cardiovascular Medical & Research Center, Tehran, Iran Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide reductase (VKOR), the target site for warfarin. The present study was conducted to investigate the association between CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms with warfarin daily dose on Iranian patients under warfarin treatment. Materials and Methods: This study is comprised of 118 Iranian patients on warfarin treatment who attended the PT Clinic. Genotyping of CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) was performed by PCR-RFLP method. Multiple regression model was performed for statistical analyses and P<0.05 was considered as significance level. Results: The allelic frequencies of CYP2C9*2 and CYP2C9*3 were 19% and 7%, respectively. Patients with ≥1 CYP2C9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. The allelic frequencies of VKORC1 were 14.4%, 57.6% and 27.9% for GG, GA, and AA genotypes, respectively. The mean (SD) warfarin daily dose in patients with the VKORC1 (–1639) GG genotype was significantly higher than GA and AA patients. Conclusion: CYP2C9*2, CYP2C9*3 and VKORC1 (-1639 G>A) polymorphisms had significant association with warfarin daily dose; furthermore, the daily warfarin dose was not influenced by age, height, weight and sex.http://rmm.mazums.ac.ir/browse.php?a_code=A-10-26-31&slc_lang=en&sid=1CYP2C9*2 CYP2C9*3 VKORC1 Warfarin RFLP |
| spellingShingle | Reyhaneh Kameli Mandana Hasanzad Zahra Tahmasebi Fard Mojgan Babanejad Mahdieh Imeni Lotfollah Feizi Barnaji Atoosa Madadkar Seyed Hamid Jamaldini Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients Research in Molecular Medicine CYP2C9*2 CYP2C9*3 VKORC1 Warfarin RFLP |
| title | Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients |
| title_full | Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients |
| title_fullStr | Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients |
| title_full_unstemmed | Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients |
| title_short | Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients |
| title_sort | association between cytochrome p450 2 c9 and vitamin k epoxide reductase complex subunit 1 polymorphisms with warfarin dose among iranian patients |
| topic | CYP2C9*2 CYP2C9*3 VKORC1 Warfarin RFLP |
| url | http://rmm.mazums.ac.ir/browse.php?a_code=A-10-26-31&slc_lang=en&sid=1 |
| work_keys_str_mv | AT reyhanehkameli associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT mandanahasanzad associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT zahratahmasebifard associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT mojganbabanejad associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT mahdiehimeni associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT lotfollahfeizibarnaji associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT atoosamadadkar associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients AT seyedhamidjamaldini associationbetweencytochromep4502c9andvitaminkepoxidereductasecomplexsubunit1polymorphismswithwarfarindoseamongiranianpatients |