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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-04

AUTHORS

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

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. More... »

PAGES

147-156

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41397-017-0005-1

DOI

http://dx.doi.org/10.1038/s41397-017-0005-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100158072

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29298995


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