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Association of the ...
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Cavallari, Larisa H.
(författare)
Association of the GGCX (CAA) 16/17 repeat polymorphism with higher warfarin dose requirements in African Americans
- Artikel/kapitelEngelska2012
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LIBRIS-ID:oai:DiVA.org:uu-168576
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-168576URI
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https://doi.org/10.1097/FPC.0b013e32834f288fDOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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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.
Ämnesord och genrebeteckningar
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African American
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gamma-glutamyl carboxylase
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warfarin
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Perera, Minoli
(författare)
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Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel
(författare)
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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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Uppsala universitetKlinisk farmakogenomik och osteoporos
(creator_code:org_t)
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Ingår i:Pharmacogenetics & Genomics22:2, s. 152-1581744-68721744-6880
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