Ardebili Seiied Moitaba Mohaddes, Yeghaneh Tarlan, Gharesouran Jalal, Rezazadeh Maryam, Farhoudi Mehdi, Ayromlou Hormoz, Talebi Mahnaz, Ghojazadeh Morteza
Associate Professor, Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
J Res Med Sci. 2011 Aug;16(8):1006-13.
Recent findings suggest that production of pro-inflammatory cytokines, such as Tumour Necrosis Factor-alpha (TNF-α), is increased in the brain tissue of patients suffering late-onset Alzheimer's disease (LOAD) and play an important role in the pathogenesis of this disease. Several epidemiological studies also suggest that patients taking anti-inflammatory drugs have a decreased risk of developing AD. TNF-α is an important pro inflammatory cytokine that is unregulated in Alzheimer's patients. Functional polymorphisms in tumor necrosis factor alpha (TNF-α) can affect immune response, inflammation, tissue injury and possibly the susceptibility to Alzheimer disease (AD).
We used the polymorphic DNA markers (-308G/A) and (-863C/A) to study the association of TNF-α gene mutations with Late-onset Alzheimer's disease (LOAD) and the relation between clinical features and genotypes in affected individuals. A total of 160 patient samples and 163 healthy controls from west northern Iran (Eastern Azerbaijan) were genotyped for the two polymorphisms by the PCR-RFLP method and genotype frequencies were statistically determined.
Our data showed significant difference in TNF-α-308 G/A genotype and pro inflammatory cytokine allele frequencies between the Alzheimer disease patients and healthy subjects. Contrary to that, no significant difference was observed in TNF-α-863 C/A genotype and allele frequencies between these two groups.
TNF-α-308 G/A gene polymorphism could affect cerebral inflammatory response and the risk of late-onset Alzheimer disease but -863 C/A polymorphism does not influence the risk of this disease and this possible association between TNF-α -308G/A and -863C/A gene polymorphisms have to be further elucidated in larger case control studies.
最近的研究结果表明，在晚发性阿尔茨海默病（LOAD）患者的脑组织中，促炎细胞因子如肿瘤坏死因子-α（TNF-α）的产生增加，并且在该疾病的发病机制中起重要作用。多项流行病学研究还表明，服用抗炎药物的患者患阿尔茨海默病的风险降低。TNF-α是一种重要的促炎细胞因子，在阿尔茨海默病患者中不受调控。肿瘤坏死因子α（TNF-α）的功能多态性可影响免疫反应、炎症、组织损伤以及可能的阿尔茨海默病（AD）易感性。
我们使用多态性DNA标记（-308G/A）和（-863C/A）来研究TNF-α基因突变与晚发性阿尔茨海默病（LOAD）的关联以及受影响个体的临床特征与基因型之间的关系。通过PCR-RFLP方法对来自伊朗西北部（东阿塞拜疆）的160例患者样本和163例健康对照进行这两种多态性的基因分型，并统计确定基因型频率。
我们的数据显示，阿尔茨海默病患者与健康受试者之间在TNF-α -308 G/A基因型和促炎细胞因子等位基因频率上存在显著差异。与此相反，在这两组之间，TNF-α -863 C/A基因型和等位基因频率未观察到显著差异。
TNF-α -308 G/A基因多态性可能影响脑部炎症反应和晚发性阿尔茨海默病的风险，但-863 C/A多态性不影响该疾病的风险，并且TNF-α -308G/A和-863C/A基因多态性之间的这种可能关联必须在更大规模的病例对照研究中进一步阐明。
