title: Lack of Association of Clinical Factors (SAMe-TT2R2) with CYP2C9/VKORC1 Genotype and Anticoagulation Control Quality.
abstract: OBJECTIVE
  Advantages of new oral anticoagulations may be greater in atrial fibrillation (AF) patients of poor anticoagulation control with warfarin. The SAMe-TT2R2 scoring system, based on clinical variables, was recently developed to aid in identifying these patients. In this study, we investigated the association of this clinical composite score with genetic factors related warfarin dosing and the quality of anticoagulation control.
  
  
  METHODS
  Clinical and genetic data were collected from 380 consecutive Korean patients with AF (CHA2DS2-VASc score, 3.5±1.8) who were followed for an average of 4 years. We evaluated factors associated with time in therapeutic range (TTR, INR 2-3), including the CYP2C9 and VKORC1 genotypes and the SAMe-TT2R2 score (Sex female, Age <60 years, Medical history [>two co-morbidities], Treatment [interacting drugs, e.g., amiodarone], Tobacco use within 2 years [doubled], and Race non-white [doubled]).
  
  
  RESULTS
  The average SAMe-TT2R2 score was 3.4±0.9, range 2-7; and 153 patients (40.2%) had SAMe-TT2R2 scores ≥4. Time in specific INR ranges varied depending on the VKORC1 genotype but not with the CYP2C9 genotype or the SAMe-TT2R2 score. TTR was higher in patients with the VKORC1 1173C>T than in VKORC1 TT (61.7±16% vs. 56.7±17.4%, P=0.031). Multivariate testing showed that VKORC1 genotype but not the SAMe-TT2R2 score was significantly associated with labile INRs. There was no correlation between the SAMe-TT2R2 scores and pharmacogenetic data.
  
  
  CONCLUSIONS
  A genetic factor, but none of the common clinical and demographic factors, as combined in the SAMe-TT2R2 score, was associated with the quality of anticoagulation control in Korean patients with AF.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mi Ji
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Suk Jae
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: June Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Bang
keywords: Atrial fibrillation; CYP2C9; International Normalized Ratio; Oral anticoagulants; Polymorphism; SAMe-TT2R2; VKORC1