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Association of the ...
Association of the GGCX (CAA) 16/17 repeat polymorphism with higher warfarin dose requirements in African Americans
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Cavallari, Larisa H. (författare)
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Perera, Minoli (författare)
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- Wadelius, Mia (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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Deloukas, Panos (författare)
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Taube, Gelson (författare)
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Patel, Shitalben R. (författare)
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Aquino-Michaels, Keston (författare)
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Viana, Marlos A. G. (författare)
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Shapiro, Nancy L. (författare)
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Nutescu, Edith A. (författare)
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 22:2, s. 152-158
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- African American
- gamma-glutamyl carboxylase
- warfarin
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- art (ämneskategori)
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Cavallari, Laris ...
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Perera, Minoli
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Wadelius, Mia
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Deloukas, Panos
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Taube, Gelson
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Patel, Shitalben ...
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visa fler...
-
Aquino-Michaels, ...
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Viana, Marlos A. ...
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Shapiro, Nancy L ...
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Nutescu, Edith A ...
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Pharmacogenetics ...
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Uppsala universitet