The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome
Aleksandra Kapedanovska-Nestorovska,1 Aleksandar J Dimovski,1,2 Zoran Sterjev,1 Nadica Matevska Geskovska,1 Ljubica Suturkova,1 Petar Ugurov,3 Zan Mitrev,4 Rodney Rosalia5 1Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic o...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2019-10-01
|
| Series: | Pharmacogenomics and Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-akr1d136-rs1872930-allelic-variant-is-independently-associated-wit-peer-reviewed-article-PGPM |
| _version_ | 1818155450863976448 |
|---|---|
| author | Kapedanovska-Nestorovska A Dimovski AJ Sterjev Z Matevska Geskovska N Suturkova L Ugurov P Mitrev Z Rosalia R |
| author_facet | Kapedanovska-Nestorovska A Dimovski AJ Sterjev Z Matevska Geskovska N Suturkova L Ugurov P Mitrev Z Rosalia R |
| author_sort | Kapedanovska-Nestorovska A |
| collection | DOAJ |
| description | Aleksandra Kapedanovska-Nestorovska,1 Aleksandar J Dimovski,1,2 Zoran Sterjev,1 Nadica Matevska Geskovska,1 Ljubica Suturkova,1 Petar Ugurov,3 Zan Mitrev,4 Rodney Rosalia5 1Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia; 2Research Center for Genetic Engineering and Biotechnology “Georgi D.Efremov”, Macedonian Academy of Sciences and Arts, Skopje, Republic of North Macedonia; 3Semi Intensive Care Unit, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 4Department of Cardiovascular Surgery, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 5Department of Clinical Research, Zan Mitrev Clinic, Skopje, Republic of North MacedoniaCorrespondence: Rodney RosaliaZan Mitrev Clinic, Bledski Dogovor #8, Skopje 1000, Republic of MacedoniaTel +389 71305957Email rodney.rosalia@zmc.mk Aleksandra Kapedanovska-NestorovskaFaculty of Pharmacy, University Ss Cyril and Methodius, Mother Theresa 47, Skopje 1000, Republic of MacedoniaTel +389 72228998Email alka@ff.ukim.edu.mkAims: The present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients.Methods: We screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57–66 years), and 55% were females.Results: The median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06).Conclusion: The AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.Keywords: AKR1D1, CYP2C19, MACCE, DAPT, clopidogrel, North Macedonia |
| first_indexed | 2024-12-11T14:42:36Z |
| format | Article |
| id | doaj.art-096c2c2bd82f4ce994f33f46fae0263e |
| institution | Directory Open Access Journal |
| issn | 1178-7066 |
| language | English |
| last_indexed | 2024-12-11T14:42:36Z |
| publishDate | 2019-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Pharmacogenomics and Personalized Medicine |
| spelling | doaj.art-096c2c2bd82f4ce994f33f46fae0263e2022-12-22T01:01:50ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662019-10-01Volume 1228729549225The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment OutcomeKapedanovska-Nestorovska ADimovski AJSterjev ZMatevska Geskovska NSuturkova LUgurov PMitrev ZRosalia RAleksandra Kapedanovska-Nestorovska,1 Aleksandar J Dimovski,1,2 Zoran Sterjev,1 Nadica Matevska Geskovska,1 Ljubica Suturkova,1 Petar Ugurov,3 Zan Mitrev,4 Rodney Rosalia5 1Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia; 2Research Center for Genetic Engineering and Biotechnology “Georgi D.Efremov”, Macedonian Academy of Sciences and Arts, Skopje, Republic of North Macedonia; 3Semi Intensive Care Unit, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 4Department of Cardiovascular Surgery, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 5Department of Clinical Research, Zan Mitrev Clinic, Skopje, Republic of North MacedoniaCorrespondence: Rodney RosaliaZan Mitrev Clinic, Bledski Dogovor #8, Skopje 1000, Republic of MacedoniaTel +389 71305957Email rodney.rosalia@zmc.mk Aleksandra Kapedanovska-NestorovskaFaculty of Pharmacy, University Ss Cyril and Methodius, Mother Theresa 47, Skopje 1000, Republic of MacedoniaTel +389 72228998Email alka@ff.ukim.edu.mkAims: The present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients.Methods: We screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57–66 years), and 55% were females.Results: The median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06).Conclusion: The AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.Keywords: AKR1D1, CYP2C19, MACCE, DAPT, clopidogrel, North Macedoniahttps://www.dovepress.com/the-akr1d136-rs1872930-allelic-variant-is-independently-associated-wit-peer-reviewed-article-PGPMAKR1D1 - CYP2C19 - MACCE - DAPT - Clopidogrel - North Macedonia |
| spellingShingle | Kapedanovska-Nestorovska A Dimovski AJ Sterjev Z Matevska Geskovska N Suturkova L Ugurov P Mitrev Z Rosalia R The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome Pharmacogenomics and Personalized Medicine AKR1D1 - CYP2C19 - MACCE - DAPT - Clopidogrel - North Macedonia |
| title | The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome |
| title_full | The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome |
| title_fullStr | The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome |
| title_full_unstemmed | The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome |
| title_short | The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome |
| title_sort | akr1d1 36 rs1872930 allelic variant is independently associated with clopidogrel treatment outcome |
| topic | AKR1D1 - CYP2C19 - MACCE - DAPT - Clopidogrel - North Macedonia |
| url | https://www.dovepress.com/the-akr1d136-rs1872930-allelic-variant-is-independently-associated-wit-peer-reviewed-article-PGPM |
| work_keys_str_mv | AT kapedanovskanestorovskaa theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT dimovskiaj theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT sterjevz theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT matevskageskovskan theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT suturkoval theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT ugurovp theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT mitrevz theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT rosaliar theakr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT kapedanovskanestorovskaa akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT dimovskiaj akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT sterjevz akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT matevskageskovskan akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT suturkoval akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT ugurovp akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT mitrevz akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome AT rosaliar akr1d136rs1872930allelicvariantisindependentlyassociatedwithclopidogreltreatmentoutcome |