Pharmacogenomics and Personalized Medicine (Oct 2019)

The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome

  • Kapedanovska-Nestorovska A,
  • Dimovski AJ,
  • Sterjev Z,
  • Matevska Geskovska N,
  • Suturkova L,
  • Ugurov P,
  • Mitrev Z,
  • Rosalia R

Journal volume & issue
Vol. Volume 12
pp. 287 – 295

Abstract

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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 [email protected] Aleksandra Kapedanovska-NestorovskaFaculty of Pharmacy, University Ss Cyril and Methodius, Mother Theresa 47, Skopje 1000, Republic of MacedoniaTel +389 72228998Email [email protected]: 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

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