Bakr Noha M, Hashim Noha A, El-Baz Hatim Alaa El-Din, Khalaf Eman Mohammad, Elharoun Ahmed Shukry
Biochemistry Department, Genetic Engineering and Biotechnology Research Division, National Research Centre (NRC), Giza, Egypt.
Neurology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Mult Scler Relat Disord. 2021 Jan;47:102654. doi: 10.1016/j.msard.2020.102654. Epub 2020 Nov 28.
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of the central nervous system (CNS). It is immunologically induced in genetically susceptible individuals. Proinflammatory cytokines play an important role as genetic polymorphisms in their genes might be involved in the susceptibility and pathogenesis of MS.
In this study, our goal was to analyze the association between the gene polymorphisms in interleukin-16 (IL-16) (rs4072111 C/T), tumor necrosis factor-α (TNF-α) -308 G/A (rs1800629 G/A) and IL-18 -607 C/A (rs1946518 C/A) and the susceptibility and clinical features of MS in an Egyptian cohort.
We genotyped these genetic polymorphisms in 150 subjects including 93 patients with MS and 57 unrelated healthy subjects. We employed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method for determining the IL-16 (rs4072111 C/T) and TNF-α -308 G/A (rs1800629 G/A) polymorphisms, and the allele- specific polymerase chain reaction (AS-PCR) method for IL-18-607 C/A (rs1946518 C/A) polymorphism.
The IL-16 (rs4072111 C/T) polymorphism was not polymorphic in both MS patients and the healthy volunteers. For the TNF-α-308 G/A (rs1800629 G/A) polymorphism, the mutant AA genotype and A allele are not associated with the susceptibility of MS, however, associated with the severity and disability progression of the disease. We observed a statistically significant increase in the mean values of Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) in patients with AA genotype and A allele compared with those of genotypes GG and GA, and the G allele, and regression analysis confirmed that this polymorphism is a predictor of disease disability using EDSS. For the IL-18 -607 C/A (rs1946518 C/A) polymorphism, the frequency of mutant AA genotype and A allele showed significant differences between the MS patients and healthy controls.
The TNF-α-308 AA genotype and A allele could be related to disability progression and severity of MS and the IL-18-607 AA genotype A allele could be related to susceptibility of the disease in the Egyptian cohort.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性和神经退行性疾病。它在遗传易感个体中由免疫诱导产生。促炎细胞因子起着重要作用，因为其基因中的遗传多态性可能与MS的易感性和发病机制有关。
在本研究中，我们的目标是分析白细胞介素-16（IL-16）（rs4072111 C/T）、肿瘤坏死因子-α（TNF-α）-308 G/A（rs1800629 G/A）和IL-18 -607 C/A（rs1946518 C/A）基因多态性与埃及队列中MS易感性和临床特征之间的关联。
我们对150名受试者进行了这些基因多态性的基因分型，其中包括93例MS患者和57名无关的健康受试者。我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法来确定IL-16（rs4072111 C/T）和TNF-α -308 G/A（rs1800629 G/A）多态性，采用等位基因特异性聚合酶链反应（AS-PCR）方法来确定IL-18-607 C/A（rs1946518 C/A）多态性。
IL-16（rs4072111 C/T）多态性在MS患者和健康志愿者中均无多态性。对于TNF-α-308 G/A（rs1800629 G/A）多态性，突变型AA基因型和A等位基因与MS的易感性无关，但与疾病的严重程度和残疾进展有关。我们观察到，与GG和GA基因型以及G等位基因相比，AA基因型和A等位基因的患者扩展残疾状态量表（EDSS）和多发性硬化症严重程度评分（MSSS）的平均值有统计学显著增加，回归分析证实，使用EDSS，这种多态性是疾病残疾的一个预测指标。对于IL-18 -607 C/A（rs1946518 C/A）多态性，突变型AA基因型和A等位基因的频率在MS患者和健康对照之间存在显著差异。
在埃及队列中，TNF-α-308 AA基因型和A等位基因可能与MS的残疾进展和严重程度有关，而IL-18-607 AA基因型和A等位基因可能与疾病的易感性有关。
