• Arch Iran Med · Oct 2020

    Functional Analysis of RELN S2486G Mutation and its Contribution to Pathogenesis of Ankylosing Spondylitis.

    • Elika Esmaeilzadeh-Gharehdaghi, Ehsan Razmara, Amirreza Bitaraf, Ahmadreza Jamshidi, Mahdi Mahmoudi, and Masoud Garshasbi.
    • Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
    • Arch Iran Med. 2020 Oct 1; 23 (10): 688-696.

    BackgroundAnkylosing spondylitis (AS; OMIM:106300) is a common complex inflammatory disease; in a previous study, we introduced a novel mutation in the RELN gene (OMIM: 600514) which was associated with AS. This study is designed to investigate the potential effect of RELN S2486G mutation on reelin secretion; additionally, we objected to evaluate the phospholipase A2 (PLA2G7) gene (OMIM: 601690) expression and platelet-activating factor-acetylhydrolase (PAF-AH) concentration as the downstream gene and the encoded protein.MethodsThe impact of the S2486G on reelin protein secretion was investigated in CHO-K1 and HEK-293T cells by constructing wild-type and mutant plasmids. Besides, the possible effect of the mutation on expression and concentration of PLA2G7 and PAF-AH in THP1 cells was assessed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The study was performed at Tarbiat Modares University, Tehran, Iran, from 2016 to 2018.ResultsOur results showed that S2486G not only causes a significant reduction in reelin secretion in both HEK-293T and CHO-K1 cells, but also it leads to a significant reduction in PLA2G7 gene expression (P value < 0.001) and protein level of PAF-AH in THP-1 cells (P value < 0.003).ConclusionThe S2486G mutation in RELN can alter inflammatory and, to some extent, osteogenesis pathways mediated by reduced secretion of reelin and also reduced expression of the PLA2G7 gene.© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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