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基因多态性与多发性硬化症的关系。

Role of and genes polymorphisms in multiple sclerosis.

机构信息

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Int J Neurosci. 2020 Apr;130(4):407-412. doi: 10.1080/00207454.2019.1694019. Epub 2019 Nov 26.

Abstract

Multiple sclerosis (MS) as a progressive chronic disease of the central nervous system (CNS) is characterized by demyelination and axonal loss. Results of genetic studies and clinical trials have proved a key role for the immune system in the pathogenesis of MS. Glucocorticoids (GR) are regarded as potent therapeutic compounds for autoimmune and inflammatory diseases which act through their receptors encoded by () gene. Meanwhile, the long non-coding RNA (lncRNA) () interacts with GR through binding to the DNA-binding domain (DBD) region and reduces GR transcriptional activity. The purpose of our study was to evaluate the association between MS and polymorphisms within (rs6189/6190, rs56149945, rs41423247) and (rs55829688) genes in 300 relapsing-remitting MS patients and 300 healthy subjects. We demonstrated significant differences in distribution of genotype, allele and haplotype frequencies of rs6189, rs41423247 and rs55829688 between the study groups. Our data may suggest that rs6189, rs41423247 and rs55829688 are associated with the increased risk of MS development. Future studies are needed to verify our results in larger sample sizes and elaborate the underlying mechanisms for contribution of these variants in MS disease.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的进行性慢性疾病,其特征是脱髓鞘和轴索丢失。遗传研究和临床试验的结果证明了免疫系统在 MS 发病机制中的关键作用。糖皮质激素(GR)被认为是治疗自身免疫和炎症性疾病的有效化合物,其通过其编码基因()基因的受体起作用。同时,长链非编码 RNA(lncRNA)()通过与 DNA 结合域(DBD)区域结合与 GR 相互作用,降低 GR 转录活性。我们研究的目的是评估 MS 与 (rs6189/6190、rs56149945、rs41423247)和 (rs55829688)基因内多态性之间的关联在 300 例复发缓解型 MS 患者和 300 例健康对照者中。我们表明,在研究组之间,rs6189、rs41423247 和 rs55829688 的基因型、等位基因和单倍型频率分布存在显著差异。我们的数据可能表明,rs6189、rs41423247 和 rs55829688 与 MS 发病风险增加相关。需要进一步的研究来验证我们在更大样本量中的结果,并阐述这些变异在 MS 疾病中的潜在机制。

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