Genetic associations with brain microbleeds Systematic review and meta-analyses

Objective: We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). Methods: We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of >100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I-2 and chi(2) statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. Results: Only the APOE epsilon 2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the epsilon 3/epsilon 3 genotype, carriers of the epsilon 4 allele (epsilon 4+) were statistically significantly more likely to have BMBs in any location (epsilon 4 + vs epsilon 3/epsilon 3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (epsilon 4 + vs epsilon 3/epsilon 3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of epsilon 4+ genotypes with strictly lobar BMBs was reasonably robust to potential publication and reporting biases. Conclusions: Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy. Neurology(R) 2011;77:158-167