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Association of the GGCX (CAA) 16/17 repeat polymorphism with higher warfarin dose requirements in African Americans
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.ORCID iD: 0000-0002-6368-2622
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2012 (English)In: Pharmacogenetics & Genomics, ISSN 1744-6872, E-ISSN 1744-6880, Vol. 22, no 2, 152-158 p.Article in journal (Refereed) Published
Abstract [en]

Objective Little is known about genetic contributors to higher than usual warfarin dose requirements, particularly for African Americans. This study tested the hypothesis that the gamma-glutamyl carboxylase (GGCX) genotype contributes to warfarin dose requirements greater than 7.5 mg/day in an African American population.

Methods A total of 338 African Americans on a stable dose of warfarin were enrolled. The GGCX rs10654848 (CAA) n, rs12714145 (G>A), and rs699664 (p.R325Q); VKORC1 c.-1639G>A and rs61162043; and CYP2C9*2, *3, *5, *8, *11, and rs7089580 genotypes were tested for their association with dose requirements greater than 7.5mg/day alone and in the context of other variables known to influence dose variability.

Results The GGCX rs10654848 (CAA) 16 or 17 repeat occurred at a frequency of 2.6% in African Americans and was overrepresented among patients requiring greater than 7.5 mg/day versus those who required lower doses (12 vs. 3%, P = 0.003; odds ratio 4.0, 95% confidence interval, 1.5-10.5). The GGCX rs10654848 genotype remained associated with high dose requirements on regression analysis including age, body size, and VKORC1 genotype. On linear regression, the GGCX rs10654848 genotype explained 2% of the overall variability in warfarin dose in African Americans. An examination of the GGCX rs10654848 genotype in warfarin-treated Caucasians revealed a (CAA) 16 repeat frequency of only 0.27% (P = 0.008 compared with African Americans).

Conclusion These data support the GGCX rs10654848 genotype as a predictor of higher than usual warfarin doses in African Americans, who have a 10-fold higher frequency of the (CAA) 16/17 repeat compared with Caucasians. Pharmacogenetics and Genomics 22: 152-158 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Place, publisher, year, edition, pages
2012. Vol. 22, no 2, 152-158 p.
Keyword [en]
African American, gamma-glutamyl carboxylase, warfarin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-168576DOI: 10.1097/FPC.0b013e32834f288fISI: 000299310600007OAI: oai:DiVA.org:uu-168576DiVA: diva2:503263
Available from: 2012-02-15 Created: 2012-02-13 Last updated: 2017-12-07

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