APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study

Objective: We aimed to examine the association of APOE e genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds.Methods: We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n 5 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study. When necessary, authors were contacted to provide effect estimates for the meta-analysis. Conclusions: APOE e4 and APOE e2 were associated with increasing burden in MRI markers for both hemorrhagic and ischemic CVD. While the association of APOE e4 with an increased burden of CVD could be partly contributing to the relationship between APOE e4 and AD, APOE e2 was associated with MRI markers of CVD in the opposite direction compared to AD. The e4 allele of the APOE gene is a major risk factor for dementia and Alzheimer disease (AD). Results 1-6The association of APOE with cerebrovascular disease (CVD) is more controversial.7 APOE e4 is a risk factor for cerebral amyloid angiopathy (CAA), a major determinant of intracerebral hemorrhage (ICH) in older individuals.1 Recent data from the International Stroke Genetics Consortium suggest an association of APOE e4 with an increased risk of ICH, mostly lobar, 8 and an association of the APOE e2 allele with an increased risk and size of lobar ICH. 8,9 Whether the epsilon polymorphism is also associated with an increased risk of ischemic stroke and MRI markers of CVD is unclear.7 MRI markers of CVD-white matter hyperintensities (WMH), brain infarcts (BI), and cerebral microbleeds (CMB)-are powerful predictors of stroke and dementia.10-13 They are highly prevalent in older community-dwelling persons, [14][15][16] and can be assessed noninvasively and quantitatively in large population-based samples. Dissecting the relationship between APOE and MRI

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“…8,9 Whether the epsilon polymorphism is also associated with an increased risk of ischemic stroke and MRI markers of CVD is unclear.…”

Section: -6mentioning

confidence: 99%

APOE genotype and MRI markers of cerebrovascular disease

et al. 2013

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“…The e2 allele is protective in Alzheimer's disease but associated with an increased risk of cerebral amyloid angiopathy-related lobar ICH. 61,62 The relationship between markers of SVD and APOE genotype was assessed by a meta-analysis of 42 cross-sectional or longitudinal studies. APOE e4 was associated with an increased burden of both WMH and microbleeds, and APOE e2 was associated with an increased WMH burden.…”

Section: Apolipoprotein Ementioning

confidence: 99%

Genetic factors in cerebral small vessel disease and their impact on stroke and dementia

Haffner

Malik

Dichgans

2015

J Cereb Blood Flow Metab

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Cerebral small vessel disease (SVD) is among the most frequent causes of both stroke and dementia. There is a growing list of genes known to be implicated in Mendelian forms of SVD. Also, genome-wide association studies have identified common variants at a number of genetic loci that are associated with manifestations of SVD, among them loci for white matter hyperintensities, small vessel stroke, and deep intracerebral hemorrhage. Driven by these discoveries and new animal models substantial progress has been made in elucidating the molecular, cellular, and physiologic mechanisms underlying SVD. A major theme emerging from these studies is the extracellular matrix (ECM). Recent findings include a role of structural constituents of the ECM such as type IV collagens in hereditary and sporadic SVD, the sequestration of proteins with a known role in ECM maintenance into aggregates of NOTCH3, and altered signaling through molecules known to interact with the ECM. Here, we review recent progress in the identification of genes involved in SVD and discuss mechanistic concepts with a particular focus on the ECM.

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“…The apolipoprotein E ε2 allele is associated with larger hematomas, which appears to explain its effect on outcome [15]. The relation between oral anticoagulation use and baseline hematoma volume is unclear; some studies have shown increased baseline volumes [16,17], whereas others have not [15,18].…”

Section: Initial Hematomamentioning

confidence: 99%

“…The observed increase is most likely due to the increased use of warfarin by patients with atrial fibrillation [58]. The use of warfarin at the time of ICH is associated with hematoma expansion [16,18] and increased mortality [15][16][17]59].…”

Section: Anticoagulation Reversalmentioning

confidence: 99%