Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose requirements in African Americans
Cavallari, Larisa H.
Patel, Shitalben R.
Viana, Marlos A.G.
Shapiro, Nancy L.
Nutescu, Edith A.
PublisherLippincott, Williams & Wilkins
MetadataShow full item record
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 γ-glutamyl carboxylase (GGCX) genotype contributes to warfarin dose requirements >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 tested for their association with dose requirements >7.5 mg/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 >7.5mg/day versus those who required lower doses (12% vs 3%, p=0.003; odds ratio 4.0, 95% CI, 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 allele frequency of only 0.27% (p=0.008 compared to 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 to Caucasians.