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. 2019 Apr;19(2):147-156.
doi: 10.1038/s41397-017-0005-1. Epub 2018 Jan 3.

Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort

Payman Shahabi  1   2   3 , Félix Lamothe  1   2   3 , Stéphanie Dumas  1   2   4 , Étienne Rouleau-Mailloux  1   2   3 , Yassamin Feroz Zada  1   2 , Sylvie Provost  1   2 , Geraldine Asselin  1   2 , Ian Mongrain  1   2 , Diane Valois  1   2 , Marie-Josée Gaulin Marion  1   2 , Louis-Philippe Lemieux Perreault  1   2 , Sylvie Perreault  4 , Marie-Pierre Dubé  5   6   7
Affiliations

Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort

Payman Shahabi et al. Pharmacogenomics J. 2019 Apr.

Abstract

Warfarin is primarily metabolized by cytochrome 2C9, encoded by gene CYP2C9. Here, we investigated whether variants in nuclear receptor genes which regulate the expression of CYP2C9 are associated with warfarin response. We used data from 906 warfarin users from the Quebec Warfarin Cohort (QWC) and tested the association of warfarin dose requirement at 3 months following the initiation of therapy in nine nuclear receptor genes: NR1I3, NR1I2, NR3C1, ESR1, GATA4, RXRA, VDR, CEBPA, and HNF4A. Three correlated SNPs in the VDR gene (rs4760658, rs11168292, and rs11168293) were associated with dose requirements of warfarin (P = 2.68 × 10-5, P = 5.81 × 10-4, and P = 5.94 × 10-4, respectively). Required doses of warfarin were the highest for homozygotes of the minor allele at the VDR variants (P < 0.0026). Variants in the VDR gene were associated with the variability in response to warfarin, emphasizing the possible clinical relevance of nuclear receptor gene variants on the inter-individual variability in drug metabolism.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram for patient inclusion in the study
See this image and copyright information in PMC

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