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17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.

ABSTRACT: BACKGROUND AND PURPOSE:Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. METHODS:We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. RESULTS:Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. CONCLUSIONS:This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.

SUBMITTER: Adib-Samii P

PROVIDER: S-EPMC3771337 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.

Adib-Samii Poneh P Rost Natalia N Traylor Matthew M Devan William W Biffi Alessandro A Lanfranconi Silvia S Fitzpatrick Kaitlin K Bevan Steve S Kanakis Allison A Valant Valerie V Gschwendtner Andreas A Malik Rainer R Richie Alexa A Gamble Dale D Segal Helen H Parati Eugenio A EA Ciusani Emilio E Holliday Elizabeth G EG Maguire Jane J Wardlaw Joanna J Worrall Bradford B Bis Joshua J Wiggins Kerri L KL Longstreth Will W Kittner Steve J SJ Cheng Yu-Ching YC Mosley Thomas T Falcone Guido J GJ Furie Karen L KL Leiva-Salinas Carlos C Lau Benison C BC Saleem Khan Muhammed M Sharma Pankaj P Fornage Myriam M Mitchell Braxton D BD Psaty Bruce M BM Sudlow Cathie C Levi Christopher C Boncoraglio Giorgio B GB Rothwell Peter M PM Meschia James J Dichgans Martin M Rosand Jonathan J Markus Hugh S HS

Stroke 20130514 6

<h4>Background and purpose</h4>Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.<h4>Methods</h4>We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMH ...[more]

PMID: 23674528

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Project description:White matter hyperintensities of presumed vascular origin (WMH) are a prevalent form of cerebral small-vessel disease and an important risk factor for post-stroke cognitive dysfunction. Despite this prevalence, it is not well understood how WMH contributes to post-stroke cognitive dysfunction. Preliminary findings suggest that increasing WMH volume is associated with total hippocampal volume in chronic stroke patients. The hippocampus, however, is a complex structure with distinct subfields that have varying roles in the function of the hippocampal circuitry and unique anatomical projections to different brain regions. For these reasons, an investigation into the relationship between WMH and hippocampal subfield volume may further delineate how WMH predispose to post-stroke cognitive dysfunction. In a prospective study of acute ischemic stroke patients with moderate/severe WMH burden, we assessed the relationship between quantitative WMH burden and hippocampal subfield volumes. Patients underwent a 3T MRI brain within 2-5 days of stroke onset. Total WMH volume was calculated in a semi-automated manner. Mean cortical thickness and hippocampal volumes were measured in the contralesional hemisphere. Total and subfield hippocampal volumes were measured using an automated, high-resolution, ex vivo computational atlas. Linear regression analyses were performed for predictors of total and subfield hippocampal volumes. Forty patients with acute ischemic stroke and moderate/severe white matter hyperintensity burden were included in this analysis. Median WMH volume was 9.0 cm3. Adjusting for intracranial volume and stroke laterality, age (β = -3.7, P < 0.001), hypertension (β = -44.7, P = 0.04), WMH volume (β = -0.89, P = 0.049), and mean cortical thickness (β = 286.2, P = 0.006) were associated with total hippocampal volume. In multivariable analysis, age (β = -3.3, P < 0.001) and cortical thickness (β = 205.2, P = 0.028) remained independently associated with total hippocampal volume. In linear regression for predictors of hippocampal subfield volume, increasing WMH volume was associated with decreased hippocampal-amygdala transition area volume (β = -0.04, P = 0.001). These finding suggest that in ischemic stroke patients, increased WMH burden is associated with selective hippocampal subfield degeneration in the hippocampal-amygdala transition area.

Dataset Information

17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.

Publications

17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.

Similar Datasets

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