Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy-Reference-Cited by-同舟云学术

Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy

Published:2016-08 Issue:13 Volume:17 Page:1425-1439
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Eriksson Niclas¹,Wallentin Lars¹,Berglund Lars¹,Axelsson Tomas²,Connolly Stuart³,Eikelboom John³,Ezekowitz Michael⁴,Oldgren Jonas¹,Paré Guillaume³,Reilly Paul⁵,Siegbahn Agneta²,Syvanen Ann-Christine²,Wadelius Claes⁶,Yusuf Salim³,Wadelius Mia²

Affiliation:

1. Uppsala Clinical Research Center & Department of Medical Sciences, Uppsala University, Uppsala, Sweden

2. Department Medical Sciences & Science for Life Laboratory, Uppsala University, Uppsala, Sweden

3. Population Health Research Institute, Hamilton Health Sciences & McMaster University, Hamilton, ON, Canada

4. Sidney Kimmel Medical Collage at Thomas Jefferson University, Philadelphia, PA, USA

5. Boehringer Ingelheim Pharma Inc, Ridgefield, CT, USA

6. Department of Immunology, Genetics & Pathology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden

Abstract

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 R2 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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2016-0061

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