The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis

Abstract

IntroductionWarfarin is the most commonly used oral anticoagulant, however, there are large interindividual variations in dose responses. Genetic polymorphisms in CYP2C9, VKORC1 and CYP4F2 have been shown to play an important role in variations in the warfarin maintenance dose in adults, but their effects in children remain unclear. We aimed to investigate the effect of VKORC1 polymorphism on warfarin dosage in pediatric patients by meta-analysis. Materials and methodsUsing strict inclusion and exclusion criteria, we searched PubMed, EMBASE, Cochrane library, Chinese Biomedical Literature Database, CNKI and ChainInfo from 2004 to Mach 17th, 2015. The relationship between warfarin dose and two single nucleotide polymorphisms of the VKORC1 gene (at positions −1639 and 1173) were analyzed using Revman version 5.2.3 software. Results and conclusionsEight studies were included in the meta-analysis, involving 610 pediatric patients. Patients that were VKORC1 −1639 GA, AA or A carriers required significantly lower warfarin dosage than GG carriers (the weighted mean difference in warfarin dose ranged from −26% to −50%). Additionally, the age of the patient and indication of warfarin (i.e. Fontan procedure) significantly affected warfarin dosage, but changes in the target international normalized ratio range had no effect. On the other hand, VKORC1 1173 polymorphisms showed no significant effect on warfarin dosage, which differs from adult patients. In conclusion, we found that VKORC1 −1639 gene polymorphisms have a moderate effect on warfarin dosage in pediatric patients, but clinical characteristics such as age and indication of warfarin also play an important role.