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. CONCLUSION: Our findings suggest that genetic effects may differ between small and large vessel subtypes, although the evidence base is small.