Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit
Objective: Genetic polymorphisms of CYP2C9 and VKORC1 play major role in pharmacokinetics and pharmacodynamics of warfarin, respectively. Purpose of our study was to assess the utility of pretesting patients for the above mutations in predicting tendency for bleeding and achieving target INR. Method...
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Elsevier
2018-12-01
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| Series: | Indian Heart Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0019483217308039 |
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| author | Mansij Biswas Shital R. Bendkhale Siddharth P. Deshpande Saket J. Thaker Dwarkanath V. Kulkarni Shobna J. Bhatia Anjali G. Rajadhyaksha Nithya J. Gogtay Urmila M. Thatte |
| author_facet | Mansij Biswas Shital R. Bendkhale Siddharth P. Deshpande Saket J. Thaker Dwarkanath V. Kulkarni Shobna J. Bhatia Anjali G. Rajadhyaksha Nithya J. Gogtay Urmila M. Thatte |
| author_sort | Mansij Biswas |
| collection | DOAJ |
| description | Objective: Genetic polymorphisms of CYP2C9 and VKORC1 play major role in pharmacokinetics and pharmacodynamics of warfarin, respectively. Purpose of our study was to assess the utility of pretesting patients for the above mutations in predicting tendency for bleeding and achieving target INR. Methods: This was an audit of data collected between July 2011 and December 2016. For safety and efficacy, patients were divided into two subgroups: those with or without bleeding and those who achieved target INR or not. Chi square test was applied to compare the between group differences and crude Odds Ratio (cOR) calculated. Results: Among 521 patients evaluated, most common indication for warfarin therapy was valvular heart disease (210/521 = 40%); 36% (187/521) had at least one bleeding episode; 56% (269/479) had below target INR. 26% (136/521) had polymorphic alleles of CYP2C9 and 69% (358/521) had the GG haplotype of VKORC1. Polymorphic alleles of CYP2C9 or AG/AA haplotype had twice the odds of bleeding (cOR = 2.14 and 2.44 respectively) relative to those with wild CYP2C9 allele or GG haplotype. Combined CYP2C9 mutant alleles and/or AG/AA haplotypes had thrice the odds of bleeding (cOR = 3.12) relative to those with wild CYP2C9 alleles and GG haplotype. Those with GG haplotype had twice the odds (cOR = 1.81) and those with GG haplotype along with wild CYP2C9 allele had four times the odds (cOR = 4.27) of not achieving the target INR relative to those with other haplotype/alleles. All these associations were statistically significant (p < 0.05). Conclusions: Pretesting patients for genetic polymorphisms could aid in individualizing warfarin therapy. Keywords: Genotype, Haplotype, Personalized medicine, Mutation, Bleeding, International Normalized Ratio (INR) |
| first_indexed | 2024-12-22T20:03:29Z |
| format | Article |
| id | doaj.art-742f466fe19d404a8fcb6280c551ceb4 |
| institution | Directory Open Access Journal |
| issn | 0019-4832 |
| language | English |
| last_indexed | 2024-12-22T20:03:29Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Indian Heart Journal |
| spelling | doaj.art-742f466fe19d404a8fcb6280c551ceb42022-12-21T18:14:12ZengElsevierIndian Heart Journal0019-48322018-12-0170S13S19Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years auditMansij Biswas0Shital R. Bendkhale1Siddharth P. Deshpande2Saket J. Thaker3Dwarkanath V. Kulkarni4Shobna J. Bhatia5Anjali G. Rajadhyaksha6Nithya J. Gogtay7Urmila M. Thatte8Department of Clinical Pharmacology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Clinical Pharmacology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Clinical Pharmacology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Clinical Pharmacology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Cardiovascular and Thoracic Surgery, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Gastroenterology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Medicine, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Clinical Pharmacology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, IndiaDepartment of Clinical Pharmacology, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, India; Corresponding author at: Department of Clinical Pharmacology, First Floor, New multi-storied Building, Seth G.S. Medical College & KEM Hospital, Acharya Donde Marg, Parel, Mumbai 400012, Maharashtra, India.Objective: Genetic polymorphisms of CYP2C9 and VKORC1 play major role in pharmacokinetics and pharmacodynamics of warfarin, respectively. Purpose of our study was to assess the utility of pretesting patients for the above mutations in predicting tendency for bleeding and achieving target INR. Methods: This was an audit of data collected between July 2011 and December 2016. For safety and efficacy, patients were divided into two subgroups: those with or without bleeding and those who achieved target INR or not. Chi square test was applied to compare the between group differences and crude Odds Ratio (cOR) calculated. Results: Among 521 patients evaluated, most common indication for warfarin therapy was valvular heart disease (210/521 = 40%); 36% (187/521) had at least one bleeding episode; 56% (269/479) had below target INR. 26% (136/521) had polymorphic alleles of CYP2C9 and 69% (358/521) had the GG haplotype of VKORC1. Polymorphic alleles of CYP2C9 or AG/AA haplotype had twice the odds of bleeding (cOR = 2.14 and 2.44 respectively) relative to those with wild CYP2C9 allele or GG haplotype. Combined CYP2C9 mutant alleles and/or AG/AA haplotypes had thrice the odds of bleeding (cOR = 3.12) relative to those with wild CYP2C9 alleles and GG haplotype. Those with GG haplotype had twice the odds (cOR = 1.81) and those with GG haplotype along with wild CYP2C9 allele had four times the odds (cOR = 4.27) of not achieving the target INR relative to those with other haplotype/alleles. All these associations were statistically significant (p < 0.05). Conclusions: Pretesting patients for genetic polymorphisms could aid in individualizing warfarin therapy. Keywords: Genotype, Haplotype, Personalized medicine, Mutation, Bleeding, International Normalized Ratio (INR)http://www.sciencedirect.com/science/article/pii/S0019483217308039 |
| spellingShingle | Mansij Biswas Shital R. Bendkhale Siddharth P. Deshpande Saket J. Thaker Dwarkanath V. Kulkarni Shobna J. Bhatia Anjali G. Rajadhyaksha Nithya J. Gogtay Urmila M. Thatte Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit Indian Heart Journal |
| title | Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit |
| title_full | Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit |
| title_fullStr | Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit |
| title_full_unstemmed | Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit |
| title_short | Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit |
| title_sort | association between genetic polymorphisms of cyp2c9 and vkorc1 and safety and efficacy of warfarin results of a 5 years audit |
| url | http://www.sciencedirect.com/science/article/pii/S0019483217308039 |
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