alexa Gamma-glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Rieder MJ, Reiner AP, Rettie AE

Abstract Share this page

Abstract BACKGROUND: The pharmacogenetic factors contributing to warfarin dosing are of great interest to clinicians, and may have utility in the management of at-risk patients prescribed warfarin. Gamma-glutamyl carboxylase (GGCX), in its role as a key component of the vitamin K cycle, is a potential candidate gene associated with warfarin treatment. OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) and correlated GGCX tagSNPs and test for association with warfarin maintenance dose. PATIENTS/METHODS: A small discovery population of European-descent individuals (n = 23) were resequenced for GGCX SNPs. Polymorphisms identified with > 5\% minor allele frequency (MAF) were genotyped in a larger clinical population of 186 European patients. Univariate, multivariate and haplotype-based linear regression were used to assess the impact of GGCX SNPs on warfarin dose. RESULTS: We identified 37 SNPs in GGCX, of which 21 were present at > 5\% MAF. These SNPs were binned, based on linkage disequilibrium, and six informative tagSNPs were identified. A single polymorphism at position 12970 (rs11676382; C/G-11\%/89\%) was associated with a warfarin maintenance dose across all analysis methods. GGCX-12970 explained 2\% of the total variance in warfarin dose, in contrast to 21 and 8\%, respectively, for VKORC1 and CYP2C9. CONCLUSIONS: The GGCX-12970 SNP had a small, but significant effect, on warfarin maintenance dose. Other polymorphisms in GGCX previously associated with warfarin dose were not confirmed in this study, suggesting that the effects of GGCX are potentially population/treatment-dependent and will not have broad utility for determining warfarin dosing. This article was published in J Thromb Haemost and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords