Association of Polymorphisms at the SIX1-SIX6 Locus With Primary Open-Angle Glaucoma.

Purpose: To evaluate the association of single-nucleotide polymorphisms (SNPs) in the SIX1-SIX6 locus with primary open-angle glaucoma (POAG) through a systematic review and meta-analysis from 22 studies. Methods: To our knowledge, all case-control association studies on SNPs in the SIX1-SIX6 locus and POAG reported up to August 30, 2018, in PubMed, Embase, and Web of Science were retrieved. Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were calculated using a fixed- or random-effect model according to interstudy heterogeneity. Results: This meta-analysis involved 12 SNPs in SIX1-SIX6 reported in 22 studies. The association of rs10483727 with POAG has been presented in 16 studies involving 14,402 patients and 27,425 controls, whereas rs33912345 has been investigated in 12 studies involving 10,563 patients and 16,740 controls. Meta-analyses revealed significant associations of these two SNPs with POAG in the pooled populations under all genetic models. Stratified analyses by population detected significant association of both SNPs in the East Asian and Caucasian subgroups, but not in South Asian or African subgroups. Among the other SNPs that were reported by up to four cohorts of East Asian and African ancestries, only rs12436579 showed a significant association in the meta-analysis (OR = 0.79, P = 1.08 × 10-4). Conclusions: This meta-analysis confirmed the association of rs10483727 and rs33912345 in SIX1-SIX6 with POAG. The associations of both SNPs were specifically detected in East Asian and Caucasian cohorts, rather than in South Asian and African cohorts, suggesting an ethnic difference. SNP rs12436579 is a candidate variant for the disease that awaits validation in other populations.

Apolipoprotein E Affects In Vitro Axonal Growth and Regeneration via the MAPK Signaling Pathway.

Following central nervous system injury in mammals, failed axonal regeneration is closely related to dysneuria. Previous studies have shown that the obvious effects of apolipoprotein E (ApoE) on traumatic brain injury (TBI) were associated with an axonal mechanism. However, little information on the actions of ApoE and its isoforms on axonal regeneration following TBI was provided. In our study, the cerebral cortices of ApoE-deficient (ApoE-/-) and wild-type (ApoE+/+) mice were cultured in vitro, and an axonal transection model was established. Interventions included the conditioned medium of astrocytes, human recombinant ApoE2/3/4 isoforms and inhibitors of the JNK/ERK/p38 pathway. Axonal growth and regeneration were evaluated by measuring the maximum distance and area of the axons. The expression levels of ß-tubulin III, MAP2, ApoE, p-JNK, p-ERK and p-p38 were detected by immunofluorescence and western blotting. The results showed that ApoE mRNA and protein were expressed in intact axons and regenerated axons. Axonal growth and regeneration were attenuated in ApoE-/- mice but recovered by exogenous ApoE. Human recombinant ApoE3 positively influenced axonal growth and regeneration; these effects were mediated by the JNK/ERK/p38 pathway. These results suggest ApoE and its isoforms may have influenced axonal growth and regeneration via the MAPK signaling pathway in vitro.