Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population

被引:50
作者
Lubitz, S. A. [1 ]
Scott, S. A. [2 ]
Rothlauf, E. B. [1 ]
Agarwal, A. [3 ]
Peter, I. [2 ]
Doheny, D. [2 ]
van der Zee, S. [1 ]
Jaremko, M. [2 ]
Yoo, C. [4 ]
Desnick, R. J. [2 ]
Halperin, J. L. [1 ]
机构
[1] Mt Sinai Sch Med, Zena & Michael Wiener Cardiovasc Inst, New York, NY USA
[2] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA
[3] Mt Sinai Sch Med, Dept Med, New York, NY USA
[4] Elmhurst Hosp, Dept Med, Queens, NY USA
关键词
CYP2C9; CYP4F2; pharmacogenetics; prediction; VKORC1; warfarin; EPOXIDE REDUCTASE COMPLEX; GAMMA-GLUTAMYL CARBOXYLASE; AFRICAN-AMERICANS; DOSE REQUIREMENT; PHARMACODYNAMIC RESISTANCE; ORAL ANTICOAGULATION; VKORC1; CYP2C9; POLYMORPHISMS; SENSITIVITY;
D O I
10.1111/j.1538-7836.2010.03792.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Gene-based warfarin dosing algorithms have largely been developed in homogeneous populations, and their generalizability has not been established. Objectives: We sought to assess the performance of published algorithms in a racially diverse and multiethnic sample, and determine if additional clinical variables or genetic variants associated with dose could enhance algorithm performance. Patients and methods: In 145 compliant patients on warfarin with a goal international normalized ratio (INR) of 2-3, stable, therapeutic doses were compared with predicted doses using 12 reported algorithms that incorporated CYP2C9 and VKORC1 variants. Additional covariates tested with each model included race, concurrent medications, medications known to interact with warfarin and previously described CYP4F2, CALU and GGCX variants. Results: The mean patient age was 67 +/- 14 years; 90 (62%) were male. Eighty-two (57%) were Caucasian, 28 (19%) African-American, 20 (14%) Hispanic and 15 (10%) Asian. The median warfarin dose was 35 mg per week (interquartile range 23-53 mg per week). Gene-based dosing algorithms explained 37-55% of the variation in warfarin dose requirements. Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms. Conclusions: Existing gene-based dosing algorithms explained between approximately one-third and one-half of the variability in warfarin dose requirements in this racially and ethnically diverse cohort. Additional clinical and recently described genetic variants associated with warfarin dose did not enhance prediction in our patient population.
引用
收藏
页码:1018 / 1026
页数:9
相关论文
共 46 条
  • [21] Klein TE, 2009, NEW ENGL J MED, V360, P753
  • [22] Validation of Clinical Testing for Warfarin Sensitivity Comparison of CYP2C9-VKORC1 Genotyping Assays and Warfarin-Dosing Algorithms
    Langley, Michael R.
    Booker, Jessica K.
    Evans, James P.
    McLeod, Howard L.
    Weck, Karen E.
    [J]. JOURNAL OF MOLECULAR DIAGNOSTICS, 2009, 11 (03) : 216 - 225
  • [23] Warfarin pharmacogenetics
    Limdi, Nita A.
    Veenstra, David L.
    [J]. PHARMACOTHERAPY, 2008, 28 (09): : 1084 - 1097
  • [24] A coding VKORC1 Asp36Tyr polymorphism predisposes to warfarin resistance
    Loebstein, Ronen
    Dvoskin, Ilana
    Halkin, Hillel
    Vecsler, Manuela
    Lubetsky, Aharon
    Rechavi, Gideon
    Amariglio, Ninette
    Cohen, Yoram
    Ken-Dror, Gie
    Almog, Shlomo
    Gak, Eva
    [J]. BLOOD, 2007, 109 (06) : 2477 - 2480
  • [25] Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients
    Miao, Liyan
    Yang, Jian
    Huang, Chenrong
    Shen, Zhenya
    [J]. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2007, 63 (12) : 1135 - 1141
  • [26] CONCURRENT AND PREDICTIVE-VALIDITY OF A SELF-REPORTED MEASURE OF MEDICATION ADHERENCE
    MORISKY, DE
    GREEN, LW
    LEVINE, DM
    [J]. MEDICAL CARE, 1986, 24 (01) : 67 - 74
  • [27] Main haplotypes and mutational analysis of vitamin K epoxide reductase (VKORC1) in a Swedish population:: a retrospective analysis of case records
    Osman, A.
    Enstrom, C.
    Arbring, K.
    Soderkvist, P.
    Lindahl, T. L.
    [J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2006, 4 (08) : 1723 - 1729
  • [28] R Development Core Team, 2016, R: A Language and Environment for Statistical Computing
  • [29] γ-Glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose
    Rieder, M. J.
    Reiner, A. P.
    Rettie, A. E.
    [J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2007, 5 (11) : 2227 - 2234
  • [30] Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose
    Rieder, MJ
    Reiner, AP
    Gage, BF
    Nickerson, DA
    Eby, CS
    McLeod, HL
    Blough, DK
    Thummel, KE
    Veenstra, DL
    Rettie, AE
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (22) : 2285 - 2293