You are here

Neurology DOI:10.1212/WNL.0000000000000816

APOE ε variants increase risk of warfarin-related intracerebral hemorrhage.

Publication TypeJournal Article
Year of Publication2014
AuthorsFalcone, GJ, Radmanesh, F, H Brouwers, B, Battey, TWK, Devan, WJ, Valant, V, Raffeld, MR, Chitsike, LP, Ayres, AM, Schwab, K, Goldstein, JN, Viswanathan, A, Greenberg, SM, Selim, M, Meschia, JF, Brown, DL, Worrall, BB, Silliman, SL, Tirschwell, DL, Flaherty, ML, Martini, SR, Deka, R, Biffi, A, Kraft, P, Woo, D, Rosand, J, Anderson, CD
Corporate AuthorsInternational Stroke Genetics Consortium
Date Published2014 Sep 23
KeywordsApolipoprotein E2, Case-Control Studies, Cerebral Hemorrhage, Genetic Predisposition to Disease, Genotype, Humans, Prospective Studies, Risk, Warfarin

OBJECTIVE: We aimed to assess the effect of APOE ε variants on warfarin-related intracerebral hemorrhage (wICH), evaluated their predictive power, and tested for interaction with warfarin in causing wICH.

METHODS: This was a prospective, 2-stage (discovery and replication), case-control study. wICH was classified as lobar or nonlobar based on the location of the hematoma. Controls were sampled from ambulatory clinics (discovery) and random digit dialing (replication). APOE ε variants were directly genotyped. A case-control design and logistic regression analysis were utilized to test for association between APOE ε and wICH. A case-only design and logistic regression analysis were utilized to test for interaction between APOE ε and warfarin. Receiver operating characteristic curves were implemented to evaluate predictive power.

RESULTS: The discovery stage included 319 wICHs (44% lobar) and 355 controls. APOE ε2 was associated with lobar (odds ratio [OR] 2.46; p 0.20). Genotyping information on APOE ε variants significantly improved case/control discrimination of lobar wICH (C statistic 0.80). No statistical interaction between warfarin and APOE was found (p > 0.20).

CONCLUSIONS: APOE ε variants constitute strong risk factors for lobar wICH. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary. Evaluation of the predictive ability of APOE in cohort studies is warranted.


Alternate JournalNeurology
PubMed ID25150286
PubMed Central IDPMC4176027
Grant ListK23 NS086873 / NS / NINDS NIH HHS / United States
P50NS061343 / NS / NINDS NIH HHS / United States
P50NS061343. / NS / NINDS NIH HHS / United States
R01 NS059727 / NS / NINDS NIH HHS / United States
NS30678 / NS / NINDS NIH HHS / United States
NS36695 / NS / NINDS NIH HHS / United States
UL1 TR001425 / TR / NCATS NIH HHS / United States
R01NS059727 / NS / NINDS NIH HHS / United States