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CYP2C9, VKORC1, and CYP4F2 polymorphisms and pediatric warfarin maintenance dose : a systematic review and meta-analysis

Takeuchi, Masanobu (author)
Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON, Canada;Yokohama City Univ, Sch Med, Dept Pediat, Yokohama, Kanagawa, Japan
Kobayashi, Tohru (author)
Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON, Canada;Natl Ctr Child Hlth & Dev, Div Clin Res Planning, Dept Dev Strategy, Ctr Clin Res & Dev, Tokyo, Japan
Biss, Tina (author)
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England;Newcastle Upon Tyne Hosp, NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England;Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Haematol, Newcastle Upon Tyne, Tyne & Wear, England
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Kamali, Farhad (author)
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England;Newcastle Upon Tyne Hosp, NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England;Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Haematol, Newcastle Upon Tyne, Tyne & Wear, England
Vear, Susan I. (author)
Nationwide Childrens Hosp, Div Pediat Hematol Oncol BMT, Columbus, OH USA
Ho, Richard H. (author)
Vanderbilt Univ, Med Ctr, Dept Pediat, Monroe Carell Jr Childrens Hosp Vanderbilt,Div Pe, Nashville, TN 37232 USA
Bajolle, Fanny (author)
Hop Necker Enfants Malad, AP HP, Unite Med Chirurg Cardiol Congenitale & Pediat, Ctr Reference M3C, Paris, France;Univ Paris 05, Paris, France
Loriot, Marie-Anne (author)
Univ Paris 05, INSERM, Unite Mixte Rech UMR S, Paris, France;Univ Paris 05, INSERM, UMR 1147, Paris, France
Shaw, Kaitlyn (author)
BC Ctr Dis Control, Influenza & Emerging Resp Pathogens, Vancouver, BC, Canada
Carleton, Bruce C. (author)
Univ British Columbia, Div Translat Therapeut, Dept Pediat, Vancouver, BC, Canada
Hamberg, Anna-Karin, 1964- (author)
Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
Wadelius, Mia (author)
Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
Hirono, Keiichi (author)
Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Pediat, Toyama, Japan
Taguchi, Masato (author)
Toyama Univ, Grad Sch Med & Pharmaceut Sci, Toyama, Japan
Wakamiya, Takuya (author)
Yokohama City Univ, Sch Med, Dept Pediat, Yokohama, Kanagawa, Japan;Kanagawa Childrens Med Ctr, Dept Cardiol, Yokohama, Kanagawa, Japan
Yanagimachi, Masakatsu (author)
Yokohama City Univ, Sch Med, Dept Pediat, Yokohama, Kanagawa, Japan;Tokyo Med & Dent Univ, Dept Pediat, Tokyo, Japan
Hirai, Keita (author)
Univ Shizuoka, Sch Pharmaceut Sci, Dept Clin Pharmacol & Genet, Shizuoka, Japan
Itoh, Kunihiko (author)
Univ Shizuoka, Sch Pharmaceut Sci, Dept Clin Pharmacol & Genet, Shizuoka, Japan
Brandao, Leonardo R. (author)
Hosp Sick Children, Div Pediat Hematol Oncol, Toronto, ON, Canada
Ito, Shinya (author)
Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON, Canada
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 (creator_code:org_t)
2019-11-01
2020
English.
In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 20:2, s. 306-319
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Research review (peer-reviewed)
Abstract Subject headings
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  • Studies on the effect of cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) polymorphisms on warfarin maintenance dose in children are conflicting. We conducted a systematic review and meta-analysis to evaluate the effect of these polymorphisms on warfarin maintenance dose in children. We searched relevant literature using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial libraries without any language restrictions from their inception to 23 July 2017. Dose differences are expressed as standardized mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CI). This review was registered in the PROSPERO prospective register of systematic reviews (CRD42015016172). We included a total of nine studies (745 participants) in the meta-analysis. Patients with CYP2C9 *1/*2, *1/*3, *2/*2, *2/*3, or *3/*3 required a lower warfarin maintenance dose compared with patients with CYP2C9 *1/*1 (SMD = -0.610, 95% CI: -0.802 to -0.419, I-2 = 0%). Patients with VKORC1-1639GA or AA required a lower warfarin maintenance dose compared with patients with VKORC1-1639GG (SMD = -0.666, 95% CI: -0.887 to -0.445, I-2 = 33%). However, no associations were observed between CYP4F2 polymorphisms and warfarin maintenance dose (MD = 0.005 mg/kg/day, 95% CI: -0.006 to 0.015, I-2 = 0%). These results were not affected by a sensitivity analysis. Our meta-analysis provides evidence that CYP2C9 and VKORC1 variant statuses affect warfarin maintenance dose in children, but not CYP4F2.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

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