Ischaemic stroke subtypes and their genetic basis: a comprehensive meta-analysis of small and large vessel stroke.
BACKGROUND
The extent to which genetic effects on the different subtypes of small (SVD) and large vessel disease (LVD) ischaemic stroke differ remains controversial.


METHODS
A comprehensive genetic meta-analysis of all genes investigated by ischaemic stroke subtype was conducted. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association.


RESULTS
From the initial search of 526 manuscripts, 5 candidate genes were studied comprising 7,533 cases (LVD 4,181, SVD 3,352) and 9,835 control subjects. There was a preferential association for SVD compared to LVD with ACE/DD (SVD: OR 1.31, 95% CI 0.96-1.79; LVD: OR 1.02, 95% CI 0.82-1.26) and eNOS intron 4 ab polymorphism (SVD: OR 1.41, 95% CI 0.94-2.11; LVD: OR 1.07, 95% CI 0.77-1.49), although statistical significance was not reached. No such preference was observed for MTHFR C677T, ApoE/epsilon4 or PAI-1 4G/5G polymorphism. The overall number of studies and the number of subjects recruited per study in whom stroke subtype was classified were small when compared to previous published work without such phenotype classification.


CONCLUSIONS
Our findings suggest that genetic effects may differ between small and large vessel subtypes, although the evidence base is small.
Rao
Rohit
R
Imperial College Cerebrovascular Research Unit, Department of Clinical Neuroscience, Imperial College London & Hammersmith Hospitals, London, UK.
Tah
Vikas
V
Casas
Juan Pablo
JP
Hingorani
Aroon
A
Whittaker
John
J
Smeeth
Liam
L
Sharma
Pankaj
P
D001057:Apolipoproteins E / Q000235:genetics; D001808:Blood Vessels / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000145:classification* / Q000235:genetics*
D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A