Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis

Innocent G. Asiimwe; Eunice J. Zhang; Rostam Osanlou; Amanda Krause; Chrisly Dillon; Guilherme Suarez-Kurtz; Honghong Zhang; Jamila A. Perini; Jessicca Y. Renta; Jorge Duconge; Larisa H. Cavallari; Leiliane R. Marcatto; Mark T. Beasly; Minoli A. Perera; Nita A. Limdi; Paulo C.J.L. Santos; Stephen E. Kimmel; Steven A. Lubitz; Stuart A. Scott; Vivian K. Kawai; Andrea L. Jorgensen; Munir Pirmohamed

doi:10.1002/cpt.1755

Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis

Innocent G. Asiimwe^*, Eunice J. Zhang, Rostam Osanlou, Amanda Krause, Chrisly Dillon, Guilherme Suarez-Kurtz, Honghong Zhang, Jamila A. Perini, Jessicca Y. Renta, Jorge Duconge, Larisa H. Cavallari, Leiliane R. Marcatto, Mark T. Beasly, Minoli A. Perera, Nita A. Limdi, Paulo C.J.L. Santos, Stephen E. Kimmel, Steven A. Lubitz, Stuart A. Scott, Vivian K. KawaiAndrea L. Jorgensen, Munir Pirmohamed

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.

Original language	English (US)
Pages (from-to)	1420-1433
Number of pages	14
Journal	Clinical pharmacology and therapeutics
Volume	107
Issue number	6
DOIs	https://doi.org/10.1002/cpt.1755
State	Published - Jun 1 2020

Funding

This research was commissioned by the National Institute for Health Research (NIHR) Global Health Research Group on Warfarin anticoagulation in patients with cardiovascular disease in sub-Saharan Africa (ref: 16/137/101) using UK aid from the UK Government. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. S.A.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. V.K.K. is funded by NIH/NIAMS K23GM117395. I.G.A. thanks the University of Liverpool for studentship funding support. This research was commissioned by the National Institute for Health Research (NIHR) Global Health Research Group on Warfarin anticoagulation in patients with cardiovascular disease in sub‐Saharan Africa (ref: 16/137/101) using UK aid from the UK Government. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. S.A.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. V.K.K. is funded by NIH/NIAMS K23GM117395.

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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10.1002/cpt.1755

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Asiimwe, I. G., Zhang, E. J., Osanlou, R., Krause, A., Dillon, C., Suarez-Kurtz, G., Zhang, H., Perini, J. A., Renta, J. Y., Duconge, J., Cavallari, L. H., Marcatto, L. R., Beasly, M. T., Perera, M. A., Limdi, N. A., Santos, P. C. J. L., Kimmel, S. E., Lubitz, S. A., Scott, S. A., ... Pirmohamed, M. (2020). Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis. Clinical pharmacology and therapeutics, 107(6), 1420-1433. https://doi.org/10.1002/cpt.1755

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title = "Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis",

abstract = "Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.",

author = "Asiimwe, {Innocent G.} and Zhang, {Eunice J.} and Rostam Osanlou and Amanda Krause and Chrisly Dillon and Guilherme Suarez-Kurtz and Honghong Zhang and Perini, {Jamila A.} and Renta, {Jessicca Y.} and Jorge Duconge and Cavallari, {Larisa H.} and Marcatto, {Leiliane R.} and Beasly, {Mark T.} and Perera, {Minoli A.} and Limdi, {Nita A.} and Santos, {Paulo C.J.L.} and Kimmel, {Stephen E.} and Lubitz, {Steven A.} and Scott, {Stuart A.} and Kawai, {Vivian K.} and Jorgensen, {Andrea L.} and Munir Pirmohamed",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors Clinical Pharmacology & Therapeutics {\textcopyright} 2019 American Society for Clinical Pharmacology and Therapeutics",

year = "2020",

month = jun,

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doi = "10.1002/cpt.1755",

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Asiimwe, IG, Zhang, EJ, Osanlou, R, Krause, A, Dillon, C, Suarez-Kurtz, G, Zhang, H, Perini, JA, Renta, JY, Duconge, J, Cavallari, LH, Marcatto, LR, Beasly, MT, Perera, MA, Limdi, NA, Santos, PCJL, Kimmel, SE, Lubitz, SA, Scott, SA, Kawai, VK, Jorgensen, AL & Pirmohamed, M 2020, 'Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis', Clinical pharmacology and therapeutics, vol. 107, no. 6, pp. 1420-1433. https://doi.org/10.1002/cpt.1755

TY - JOUR

T1 - Genetic Factors Influencing Warfarin Dose in Black-African Patients

T2 - A Systematic Review and Meta-Analysis

AU - Asiimwe, Innocent G.

AU - Zhang, Eunice J.

AU - Osanlou, Rostam

AU - Krause, Amanda

AU - Dillon, Chrisly

AU - Suarez-Kurtz, Guilherme

AU - Zhang, Honghong

AU - Perini, Jamila A.

AU - Renta, Jessicca Y.

AU - Duconge, Jorge

AU - Cavallari, Larisa H.

AU - Marcatto, Leiliane R.

AU - Beasly, Mark T.

AU - Perera, Minoli A.

AU - Limdi, Nita A.

AU - Santos, Paulo C.J.L.

AU - Kimmel, Stephen E.

AU - Lubitz, Steven A.

AU - Scott, Stuart A.

AU - Kawai, Vivian K.

AU - Jorgensen, Andrea L.

AU - Pirmohamed, Munir

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.

AB - Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.

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Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis

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