Interpretation of the effect of CYP2C9, VKORC1 and CYP4F2 variants on warfarin dosing adjustment in Turkey

Kocael A., Eronat A. P., Tuzuner M. B., Ekmekci A., Orhan A. L., Ikizceli I., ...Daha Fazla

MOLECULAR BIOLOGY REPORTS, cilt.46, sa.2, ss.1825-1833, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 46 Sayı: 2
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1007/s11033-019-04634-9
  • Dergi Adı: MOLECULAR BIOLOGY REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1825-1833
  • Anahtar Kelimeler: Warfarin dosing, Drug sensitivity, Pharmacogenetics, NORMALIZED RATIO CONTROL, DOSE REQUIREMENTS, ATRIAL-FIBRILLATION, TURKISH POPULATION, GENETIC-VARIANTS, POLYMORPHISMS, IMPACT, ASSOCIATION, GENOTYPE, JAPANESE
  • İstanbul Üniversitesi Adresli: Evet

Özet

It was aimed to underline the importance and explain the meaning of genetic testing in warfarin dosing and investigate and evaluate the contributions of the CYP2C9, VKORC1, and CYP4F2 variants in a Turkish population. Two hundred patients were genotyped for CYP2C9 (rs1799853, rs1057910 and rs56165452), VKORC1 (rs9934438, rs8050894, rs9923231, rs7294 and rs2359612) and CYP4F2 (rs2108622), yet, only 127 patients were found suitable for further evaluation in terms of their personal response to warfarin due to long term usage and available INR and dose usage information. The DNA sequences were determined by the ABI PRISM 3100 Genetic Analyzer to 3130xl System (Applied Biosystems, Foster City, California). Warfarin dose application suggestions by warfaringdosing.org, FDA and MayoClinic were followed. Dose requirements in the Turkish population were found higher than the suggested doses by warfarindosing.org. The multivariate logistic regression analysis reveals the utilization of VCORC1 genetic evaluation is valuable in warfarin dosing (low and moderate vs. high) in this study (p<0.001). The present study provides findings for clinicians to adapt the genetic data to the daily practice. We observed that the VKORC1 variant showed a more potent impact in warfarin dosing in this study.