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P1‐145: HOW DOES OVER‐EXPRESSION OF ALPHA SYNUCLEIN ALTER THE RELEASE OF NEUROTROPHIC FACTORS AND THEIR RECEPTORS IN DIFFERENTIATED SH‐SY5Y CELLS?
Author(s) -
Şengül Büşra,
Dursun Erdinc,
Gezen-Ak Duygu
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.700
Subject(s) - sh sy5y , microbiology and biotechnology , neurotrophic factors , biology , alpha synuclein , neurotrophin , receptor , secretion , endocrinology , cell culture , medicine , biochemistry , neuroblastoma , genetics , disease , parkinson's disease
Family-based Quasi-likelihood Score test (Won et al, 2015, BMC Bioinformatics). This approach, implented in the ONETOOL program (Song et al, 2018, Bioinformatics), incorporates a unique test statistc that considers heterogeneity of effect due to ascertainment bias among family members and. Analyses were performed using a regression model that included a term for the SNP and covariates for sex, and age. We also tested association within APOE4 carriers (E4+) and noncarriers (E4-) respectively. Results: The most significant association was observed with several SNPs near EPHA6 including rs7611319 (P1⁄43.19x10), rs1433241 (P1⁄44.44x10), rs6438286 (P1⁄44.99x10) and rs1560741 (P1⁄45.48x10). But, these SNPs are not significant in the APOE subgroup analysis, the pattern of association was similar within them. However, there are suggestive findings in APOE E4group including rs13124088 (ATP8A1, P1⁄41.14x10), rs1805543 (GRIN2B, P1⁄43.52x10), and rs11055557 (GRIN2B, P1⁄43.87x10). Conclusions: EPHA6 is a member of the Eph receptor tyrosine kinase family that mediates axon guidance with bidirectional signaling into neighboring cells, including EPHA1, which is a previously established AD risk gene. Furthermore, Ephs and ephrins have been found to play a role in neuronal morphogenesis and synaptic transmission, including memory formation and retention. Our findings suggest that family-based analysis with MFQLS method is a useful approach to identifying novel genetic associations with complex diseases.