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Published on: September 9, 2012
Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy
Niclas Eriksson1, Lars Wallentin1, Lars Berglund1
1Uppsala Clinical Research Center & Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Aims:
We investigated associations between genetic variation in candidate genes and on a genome-wide scale with warfarin maintenance dose, time in therapeutic range (TTR), and risk of major bleeding.
Materials & Methods:
In total, 982 warfarin-treated patients from the RE-LY trial were studied.
Results:
After adjusting for SNPs in VKORC1 and CYP2C9, SNPs in DDHD1 (rs17126068) and NEDD4 (rs2288344) were associated with dose. Adding these SNPs and CYP4F2 (rs2108622) to a base model increased R(2) by 2.9%. An SNP in ASPH (rs4379440) was associated with TTR (-6.8% per minor allele). VKORC1 was associated with time less than INR 2.0. VKORC1 and CYP2C9 were associated with time more than INR 3.0, but not with major bleeding.
Conclusions:
We identified two novel genes associated with warfarin maintenance dose and one gene associated with TTR. These genes need to be replicated in an independent cohort.
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