TY - JOUR
T1 - CYP2C9, VKORC1, and CYP4F2 polymorphisms and pediatric warfarin maintenance dose
T2 - a systematic review and meta-analysis
AU - Takeuchi, Masanobu
AU - Kobayashi, Tohru
AU - Biss, Tina
AU - Kamali, Farhad
AU - Vear, Susan I.
AU - Ho, Richard H.
AU - Bajolle, Fanny
AU - Loriot, Marie Anne
AU - Shaw, Kaitlyn
AU - Carleton, Bruce C.
AU - Hamberg, Anna Karin
AU - Wadelius, Mia
AU - Hirono, Keiichi
AU - Taguchi, Masato
AU - Wakamiya, Takuya
AU - Yanagimachi, Masakatsu
AU - Hirai, Keita
AU - Itoh, Kunihiko
AU - Brandão, Leonardo R.
AU - Ito, Shinya
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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, I2 = 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, I2 = 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, I2 = 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.
AB - 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, I2 = 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, I2 = 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, I2 = 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.
UR - http://www.scopus.com/inward/record.url?scp=85074712292&partnerID=8YFLogxK
U2 - 10.1038/s41397-019-0117-x
DO - 10.1038/s41397-019-0117-x
M3 - 学術論文
C2 - 31673144
AN - SCOPUS:85074712292
SN - 1470-269X
VL - 20
SP - 306
EP - 319
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 2
ER -