AIM: To determine whether genetic variants associated with warfarin dose variability were associated with increased risk of major bleeding during warfarin therapy. MATERIALS & METHODS: Using Vanderbilt's DNA biobank we compared the prevalence of CYP2C9, VKORC1 and CYP4F2 variants in 250 cases with major bleeding and 259 controls during warfarin therapy. RESULTS: CYP2C9*3 was the only allele that differed significantly among cases (14.2%) and controls (7.8%; p = 0.022). In the 214 (85.6%) cases with a major bleed 30 or more days after warfarin initiation, CYP2C9*3 was the only variant associated with bleeding (adjusted odds ratio: 2.05; 95% CI: 1.04, 4.04). CONCLUSION: The CYP2C9*3 allele may double the risk of major bleeding among patients taking warfarin for 30 or more days.
AIM: To determine whether genetic variants associated with warfarin dose variability were associated with increased risk of major bleeding during warfarin therapy. MATERIALS & METHODS: Using Vanderbilt's DNA biobank we compared the prevalence of CYP2C9, VKORC1 and CYP4F2 variants in 250 cases with major bleeding and 259 controls during warfarin therapy. RESULTS:CYP2C9*3 was the only allele that differed significantly among cases (14.2%) and controls (7.8%; p = 0.022). In the 214 (85.6%) cases with a major bleed 30 or more days after warfarin initiation, CYP2C9*3 was the only variant associated with bleeding (adjusted odds ratio: 2.05; 95% CI: 1.04, 4.04). CONCLUSION: The CYP2C9*3 allele may double the risk of major bleeding among patients taking warfarin for 30 or more days.
Entities:
Keywords:
CYP2C9; CYP4F2; VKORC1; pharmacogenetics; risk of major bleeding; warfarin
Authors: J A Roth; D Boudreau; M M Fujii; F M Farin; A E Rettie; K E Thummel; D L Veenstra Journal: Clin Pharmacol Ther Date: 2014-02-06 Impact factor: 6.875
Authors: Benjamin D Horne; Petra A Lenzini; Mia Wadelius; Andrea L Jorgensen; Stephen E Kimmel; Paul M Ridker; Niclas Eriksson; Jeffrey L Anderson; Munir Pirmohamed; Nita A Limdi; Robert C Pendleton; Gwendolyn A McMillin; James K Burmester; Daniel Kurnik; C Michael Stein; Michael D Caldwell; Charles S Eby; Anders Rane; Jonatan D Lindh; Jae-Gook Shin; Ho-Sook Kim; Pantep Angchaisuksiri; Robert J Glynn; Kathryn E Kronquist; John F Carlquist; Gloria R Grice; Robert L Barrack; Juan Li; Brian F Gage Journal: Thromb Haemost Date: 2011-12-21 Impact factor: 5.249
Authors: Stephen E Kimmel; Benjamin French; Scott E Kasner; Julie A Johnson; Jeffrey L Anderson; Brian F Gage; Yves D Rosenberg; Charles S Eby; Rosemary A Madigan; Robert B McBane; Sherif Z Abdel-Rahman; Scott M Stevens; Steven Yale; Emile R Mohler; Margaret C Fang; Vinay Shah; Richard B Horenstein; Nita A Limdi; James A S Muldowney; Jaspal Gujral; Patrice Delafontaine; Robert J Desnick; Thomas L Ortel; Henny H Billett; Robert C Pendleton; Nancy L Geller; Jonathan L Halperin; Samuel Z Goldhaber; Michael D Caldwell; Robert M Califf; Jonas H Ellenberg Journal: N Engl J Med Date: 2013-11-19 Impact factor: 91.245
Authors: R Loebstein; H Yonath; D Peleg; S Almog; M Rotenberg; A Lubetsky; J Roitelman; D Harats; H Halkin; D Ezra Journal: Clin Pharmacol Ther Date: 2001-08 Impact factor: 6.875
Authors: Andrea H Ramirez; Yaping Shi; Jonathan S Schildcrout; Jessica T Delaney; Hua Xu; Matthew T Oetjens; Rebecca L Zuvich; Melissa A Basford; Erica Bowton; Min Jiang; Peter Speltz; Raquel Zink; James Cowan; Jill M Pulley; Marylyn D Ritchie; Daniel R Masys; Dan M Roden; Dana C Crawford; Joshua C Denny Journal: Pharmacogenomics Date: 2012-02-13 Impact factor: 2.533
Authors: Kirstin Lund; Dairena Gaffney; Richard Spooner; Anne Marie Etherington; Patrick Tansey; Robert Campbell Tait Journal: Br J Haematol Date: 2012-05-10 Impact factor: 6.998
Authors: Munir Pirmohamed; Girvan Burnside; Niclas Eriksson; Andrea L Jorgensen; Cheng Hock Toh; Toby Nicholson; Patrick Kesteven; Christina Christersson; Bengt Wahlström; Christina Stafberg; J Eunice Zhang; Julian B Leathart; Hugo Kohnke; Anke H Maitland-van der Zee; Paula R Williamson; Ann K Daly; Peter Avery; Farhad Kamali; Mia Wadelius Journal: N Engl J Med Date: 2013-11-19 Impact factor: 91.245
Authors: Otito F Iwuchukwu; Andrea H Ramirez; Yaping Shi; Erica A Bowton; Vivian K Kawai; Jonathan S Schildcrout; Dan M Roden; Joshua C Denny; C Michael Stein Journal: Pharmacogenet Genomics Date: 2016-11 Impact factor: 2.089
Authors: Nita A Limdi; Todd M Brown; Aditi Shendre; Nianjun Liu; Charles E Hill; Timothy M Beasley Journal: Pharmacogenet Genomics Date: 2017-10 Impact factor: 2.089
Authors: Eitan A Friedman; Luisa Texeira; Jessica Delaney; Peter E Weeke; Donald R Lynch; Ehab Kasasbeh; Yanna Song; Frank E Harrell; Josh C Denny; Heidi E Hamm; Dan M Roden; John H Cleator Journal: J Thromb Thrombolysis Date: 2016-05 Impact factor: 2.300
Authors: Innocent G Asiimwe; Eunice J Zhang; Rostam Osanlou; Amanda Krause; Chrisly Dillon; Guilherme Suarez-Kurtz; Honghong Zhang; Jamila A Perini; Jessicca Y Renta; Jorge Duconge; Larisa H Cavallari; Leiliane R Marcatto; Mark T Beasly; Minoli A Perera; Nita A Limdi; Paulo C J L Santos; Stephen E Kimmel; Steven A Lubitz; Stuart A Scott; Vivian K Kawai; Andrea L Jorgensen; Munir Pirmohamed Journal: Clin Pharmacol Ther Date: 2020-01-28 Impact factor: 6.875