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埃及人群队列中miR-155和miR-146a基因多态性与多发性硬化易感性的关系

Relationship between miR-155 and miR-146a polymorphisms and susceptibility to multiple sclerosis in an Egyptian cohort.

作者信息

Ahmed Ali Marwa, Gamil Shaker Olfat, Mohamed Eid Hanaa, Elsayed Mahmoud Eman, Mahmoud Ezzat Eman, Nady Gaber Sylvana

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum 63514, Egypt.

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.

出版信息

Biomed Rep. 2020 May;12(5):276-284. doi: 10.3892/br.2020.1286. Epub 2020 Mar 4.

Abstract

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. It was previously demonstrated that miR-155 and miR-146a served a vital role in the pathophysiology of MS, and single nucleotide polymorphisms in miR-155 and miR-146a were found to be associated with the susceptibility to different autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type I diabetes. The aim of the present study was to analyze the association between susceptibility to MS and two genetic polymorphisms (miR-155 rs767649 A>T and miR-146a rs57095329 A>G) in a cohort of Egyptian patients. The presence of the two polymorphisms were analyzed in 114 patients with MS and 152 healthy controls using quantitative PCR. The present study demonstrated for the first time that: The TT genotype and T allele in miR-155 (rs767649 A>T) polymorphism were associated with an increased risk of MS; the miR-146a (rs57095329 A>G) mutated G allele conferred protection against the development of MS in all genetic models; miR-155 rs767649 A>T was a risk associated polymorphism of MS in females, but not in males; and miR-155 rs767649 AT/TT and miR-146a rs57095329 GG genotypes showed significantly higher distributions among patients with higher Expanded Disability Status Scale scores and secondary progressive MS subgroups. Therefore, miR-155 rs767649 polymorphism may confer susceptibility to MS, whereas miR-146a rs57095329 may be protective against MS in an Egyptian cohort.

摘要

多发性硬化症(MS)是一种中枢神经系统的自身免疫性疾病。先前的研究表明,miR-155和miR-146a在MS的病理生理学中起着至关重要的作用,并且发现miR-155和miR-146a中的单核苷酸多态性与不同自身免疫性疾病的易感性相关,如系统性红斑狼疮、类风湿性关节炎和I型糖尿病。本研究的目的是分析埃及患者队列中MS易感性与两种基因多态性(miR-155 rs767649 A>T和miR-146a rs57095329 A>G)之间的关联。使用定量PCR分析了114例MS患者和152例健康对照中这两种多态性的存在情况。本研究首次表明:miR-155(rs767649 A>T)多态性中的TT基因型和T等位基因与MS风险增加相关;miR-146a(rs57095329 A>G)突变的G等位基因在所有遗传模型中均对MS的发生具有保护作用;miR-155 rs767649 A>T是女性MS的风险相关多态性,但在男性中不是;miR-155 rs767649 AT/TT和miR-146a rs57095329 GG基因型在扩展残疾状态量表评分较高的患者和继发进展型MS亚组中分布显著更高。因此,在埃及队列中,miR-155 rs767649多态性可能赋予MS易感性,而miR-146a rs57095329可能对MS具有保护作用。

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