Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans

被引：56

作者：

Hernandez, W. ^{[1
]}

Gamazon, E. R. ^{[1
]}

Aquino-Michaels, K. ^{[1
]}

Patel, S. ^{[2
]}

O'Brien, T. J. ^{[3
]}

Harralson, A. F. ^{[3
,4
]}

Kittles, R. A. ^{[5
]}

Barbour, A. ^{[6
]}

Tuck, M. ^{[7
]}

McIntosh, S. D. ^{[6
,7
]}

Douglas, J. N. ^{[7
]}

Nicolae, D. ^{[1
]}

Cavallari, L. H. ^{[2
]}

Perera, M. A. ^{[1
]}

机构：

[1] Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL 60637 USA

[2] Univ Illinois, Dept Pharm, Chicago, IL USA

[3] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC USA

[4] Shenandoah Univ, Bernard J Dunn Sch Pharm, Dept Pharmacogenom, Ashburn, VA USA

[5] Univ Illinois, Dept Med, Inst Human Genet, Chicago, IL USA

[6] George Washington Univ, Dept Med, Washington, DC USA

[7] Uniformed Serv Univ Hlth Sci, Dept Vet Affairs, Washington, DC USA

来源：

PHARMACOGENOMICS JOURNAL | 2014年 / 14卷 / 03期

关键词：

African Americans; algorithm; CYP2C9; polymorphisms; VKORC1; warfarin; DOSE REQUIREMENTS; VKORC1; CYP2C9; RISK; POLYMORPHISM; ASSOCIATION; PROPORTIONS; ALGORITHMS; HAPLOTYPES; DABIGATRAN;

D O I：

10.1038/tpj.2013.34

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R-2=0.27) than the IWPC pharmacogenomics (R-2=0.15) or clinical (R-2=0.16) algorithms. Among high-dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC pharmacogenomics and clinical algorithms, respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry was observed for the IWPC pharmacogenomics algorithm among patients requiring >= 60 mg per week (beta = -2.04, P=0.02).

引用

页码：223 / 228

页数：6

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