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Thromb Haemost 2010; 104(04): 750-754
DOI: 10.1160/TH09-11-0763
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Gamma-glutamyl carboxylase and its influence on warfarin dose

Cristi R. King
1   Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
,
Elena Deych
1   Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
,
Paul Milligan
1   Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
,
Charles Eby
1   Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
2   Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA
,
Petra Lenzini
1   Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
,
Gloria Grice
3   St. Louis College of Pharmacy, Saint Louis, Missouri, USA
,
Rhonda M. Porche-Sorbet
2   Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA
,
Paul M. Ridker
4   Brigham and Women‘s Hospital, Harvard Medical School, Boston, Massachusetts, USA
,
Brian F. Gage
1   Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
› Author Affiliations Financial support:This study was supported by the NIH (R01 HL074724, R01 HL097036, R01 HL57951, R01 HL58036) and the American Heart Association.
Further Information

Publication History

Received: 10 November 2009

Accepted after major revision: 08 June 2010

Publication Date:
24 November 2017 (online)

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Summary

Via generation of vitamin K-dependent proteins, gamma-glutamyl carboxylase (GGCX) plays a critical role in the vitamin K cycle. Single nucleotide polymorphisms (SNPs) in GGCX, therefore, may affect dosing of the vitamin K antagonist, warfarin. In a multi-centered, cross-sectional study of 985 patients prescribed warfarin therapy, we genotyped for two GGCX SNPs (rs11676382 and rs12714145) and quantified their relationship to therapeutic dose. GGCX rs11676382 was a significant (p=0.03) predictor of residual dosing error and was associated with a 6.1% reduction in warfarin dose (95% CI: 0.6%-11.4%) per G allele. The prevalence was 14.1% in our predominantly (78%) Caucasian cohort, but the overall contribution to dosing accuracy was modest (partial R2 = 0.2%). GGCX rs12714145 was not a significant predictor of therapeutic dose (p = 0.26). GGCX rs11676382 is a statistically significant predictor of warfarin dose, but the clinical relevance is modest. Given the potentially low marginal cost of adding this SNP to existing geno-typing platforms, we have modified our non-profit website (www.WarfarinDosing.org) to accommodate knowledge of this variant.

Keywords

Gamma-glutamyl carboxylase - warfarin - pharmacogenetics - algorithm
 

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