OBJECTIVE: Patients with brain arteriovenous malformation (AVM) are at life-threatening risk of intracranial hemorrhage (ICH). Identification of genetic variants associated with increased new ICH risk would facilitate risk stratification and guide therapeutic intervention. METHODS: Brain AVM patients evaluated at University of California, San Francisco or Kaiser Permanente Northern California were followed longitudinally. Primary outcome was new ICH after diagnosis; censoring events were any AVM treatment or last follow-up examination. The association of ApoE epsilon2 and epsilon4 genotype with new ICH was evaluated by Kaplan-Meier survival analysis and further characterized via a Cox proportional hazards model. RESULTS: We genotyped 284 brain AVM patients (50% women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a history of new ICH). ApoE epsilon2, but not ApoE epsilon4 genotype, was associated with new ICH (P = 0.0052). ApoE epsilon2 carriers had fivefold increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46-17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and clinical presentation). Subset analysis in the largest homogenous ethnic subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE epsilon2 carriers (hazard ratio, 8.71; 95% confidence interval, 1.4-53.9; P = 0.020; multivariate model adjusting for clinical presentation). CONCLUSION: ApoE genotype may influence the risk of ICH in the natural course of brain AVM. The identification of genetic predictors of ICH risk may facilitate estimation of AVM natural history risk and individualize clinical decision-making and therapeutic recommendations.
OBJECTIVE:Patients with brain arteriovenous malformation (AVM) are at life-threatening risk of intracranial hemorrhage (ICH). Identification of genetic variants associated with increased new ICH risk would facilitate risk stratification and guide therapeutic intervention. METHODS: Brain AVM patients evaluated at University of California, San Francisco or Kaiser Permanente Northern California were followed longitudinally. Primary outcome was new ICH after diagnosis; censoring events were any AVM treatment or last follow-up examination. The association of ApoE epsilon2 and epsilon4 genotype with new ICH was evaluated by Kaplan-Meier survival analysis and further characterized via a Cox proportional hazards model. RESULTS: We genotyped 284 brain AVM patients (50% women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a history of new ICH). ApoE epsilon2, but not ApoE epsilon4 genotype, was associated with new ICH (P = 0.0052). ApoE epsilon2 carriers had fivefold increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46-17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and clinical presentation). Subset analysis in the largest homogenous ethnic subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE epsilon2 carriers (hazard ratio, 8.71; 95% confidence interval, 1.4-53.9; P = 0.020; multivariate model adjusting for clinical presentation). CONCLUSION:ApoE genotype may influence the risk of ICH in the natural course of brain AVM. The identification of genetic predictors of ICH risk may facilitate estimation of AVM natural history risk and individualize clinical decision-making and therapeutic recommendations.
Authors: R P Atkinson; I A Awad; H H Batjer; C F Dowd; A Furlan; S L Giannotta; C R Gomez; D Gress; G Hademenos; V Halbach; J C Hemphill; R T Higashida; L N Hopkins; M B Horowitz; S C Johnston; M W Lawton; M W McDermott; A M Malek; J P Mohr; A I Qureshi; H Riina; W S Smith; J Pile-Spellman; R F Spetzler; T A Tomsick; W L Young Journal: Stroke Date: 2001-06 Impact factor: 7.914
Authors: Tomoki Hashimoto; Gen Wen; Michael T Lawton; Nancy J Boudreau; Andrew W Bollen; Guo-Yuan Yang; Nicholas M Barbaro; Randall T Higashida; Christopher F Dowd; Van V Halbach; William L Young Journal: Stroke Date: 2003-03-20 Impact factor: 7.914
Authors: June E Eichner; S Terence Dunn; Ghazala Perveen; David M Thompson; Kenneth E Stewart; Berrit C Stroehla Journal: Am J Epidemiol Date: 2002-03-15 Impact factor: 4.897
Authors: H Mast; W L Young; H C Koennecke; R R Sciacca; A Osipov; J Pile-Spellman; L Hacein-Bey; H Duong; B M Stein; J P Mohr Journal: Lancet Date: 1997-10-11 Impact factor: 79.321
Authors: M O McCarron; C J Weir; K W Muir; K L Hoffmann; C Graffagnino; J A R Nicoll; K R Lees; M J Alberts Journal: Acta Neurol Scand Date: 2003-02 Impact factor: 3.209
Authors: Alexander X Halim; Vineeta Singh; S Claiborne Johnston; Randall T Higashida; Christopher F Dowd; Van V Halbach; Michael T Lawton; Daryl R Gress; Charles E McCulloch; William L Young Journal: Stroke Date: 2002-03 Impact factor: 7.914
Authors: Joseph F Clark; Daniel A Huri; Janice Carrozzella; Edward C Jauch; Pritesh Mehta; Daniel Heaton; Susan J Biehle; Joseph P Broderick Journal: Front Biosci Date: 2002-08-01
Authors: J van Beijnum; H B van der Worp; H M Schippers; O van Nieuwenhuizen; L J Kappelle; G J E Rinkel; J W Berkelbach van der Sprenkel; C J M Klijn Journal: J Neurol Neurosurg Psychiatry Date: 2007-01-26 Impact factor: 10.154
Authors: Helen Kim; Charles E McCulloch; S Claiborne Johnston; Michael T Lawton; Stephen Sidney; William L Young Journal: Am J Epidemiol Date: 2010-05-14 Impact factor: 4.897
Authors: Achal S Achrol; Helen Kim; Ludmila Pawlikowska; K Y Trudy Poon; Charles E McCulloch; Nerissa U Ko; S Claiborne Johnston; Michael W McDermott; Jonathan G Zaroff; Michael T Lawton; Pui-Yan Kwok; William L Young Journal: Neurosurgery Date: 2007-10 Impact factor: 4.654