Apolipoprotein E ε4 Polymorphism as a Risk Factor for Ischemic Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack of a large sample size of researches. This meta-analysis was performed to explore the potential association between the APOE gene and IS. METHODS: To identify relevant case control studies in English publications by October 2020, we searched PubMed, Embase, Web of Science, and the Cochrane Library. Pooled odds ratios (ORs) with fixed- or random-effect models and corresponding 95% confidence intervals (CIs) were calculated to analyze potential associations. RESULTS: A total of 55 researches from 32 countries containing 12207 IS cases and 27742 controls were included. The association between APOE gene ε4 mutation and IS was confirmed (ε4 vs. ε3 allele: pooled OR = 1.374, 95% CI, 1.214-1.556; ε2/ε4 vs. ε3/ε3: pooled OR = 1.233, 95% CI, 1.056-1.440; ε3/ε4 vs. ε3/ε3: pooled OR = 1.340, 95% CI, 1.165-1.542; ε4/ε4 vs. ε3/ε3: pooled OR = 1.833, 95% CI, 1.542-2.179; and APOE ε4 carriers vs. non-ε4 carriers: pooled OR = 1.377; 95% CI, 1.203-1.576). Interestingly, APOE ε4 mutation showed a dose-response correlation with IS risk (ε4/ε4 vs. ε2/ε4: pooled OR = 1.625; 95% CI, 1.281-2.060; ε4/ε4 vs. ε3/ε4: pooled OR = 1.301; 95% CI, 1.077-1.571). Similar conclusions were drawn in the small artery disease (SAD) subtype, but not in large artery atherosclerosis (LAA) or in cardioaortic embolism (CE), by subgroup analysis. CONCLUSIONS: These observations reveal that specific APOE ε4 mutation was significantly associated with the risk of IS in a dose-dependent manner, while APOE ε4 mutation was related to SAD subtype onset without a cumulative effect.

Dynamic changes of peripheral blood lymphocyte subsets in acute ischemic stroke and prognostic value.

OBJECTIVE: To explore dynamic changes of peripheral blood lymphocyte subsets in patients with acute ischemic stroke (AIS) and the relationship with stroke severity and long-term outcomes. METHODS: A total of 96 consecutive patients with AIS and 28 age- and gender-matched healthy controls were recruited. Peripheral blood samples were collected, and the percentages of lymphocyte subsets were analyzed by flow cytometry. The dynamic changes in lymphocyte subsets and their correlation with clinical parameters, such as National Institutes of Health Stroke Scale (NIHSS) scores at onset and modified Rankin scale (mRS) scores 3 months later, were evaluated. RESULTS: In our study, we observed a decrease in the percentages of T-lymphocytes (T cells), helper/inducible T-lymphocytes (Th cells) and suppressor/cytotoxic T-lymphocytes (Ts cells) in AIS patients as compared to controls. The frequencies of T cells and Ts cells on day 8-14 after stroke in NIHSS ≤4 group were significantly higher than those in NIHSS >4 group. The percentages of T cells and Th cells on day 1-3 after stroke in the mRS ≤2 group were higher than those in the mRS >2 group. CONCLUSION: The frequencies of T cells, Th cells, and Ts cells in AIS are declined dramatically at least 14 days after stroke. Lower frequencies of T cells and Ts cells on day 8-14 after stroke represent more severe disease conditions, and the percentages of T cells and Th cells within 72 hr after stroke are negatively correlated with 3-month outcomes, which might have a potential for predicting long-term prognosis of stroke.