Abstract

In Alzheimer’s disease, which is characterized by amyloid plaques and neurofibrillary tangles in the brain tissue, many components such as acute phase proteins, cytokines, and proteases contribute to the progression of the disease or are part of the pathological process. The macrophage migration inhibitory factor (MIF) gene encodes a cytokine, which is secreted by lymphocytes, and has a role in the pathogenesis of autoimmune/inflammatory diseases such as rheumatoid arthritis. The purpose of this study to investigate the association between Alzheimer disease and MIF gene promoter polymorphisms. The 205 patients with Alzheimer disease (AD) and 130 age-sex matched healthy individuals were investigated in terms of MIF -173 G/C and MIF −794 CATT polymorphisms. The genotyping of MIF -173 G/C was determined using the RT-PCR method. MIF-794 CATT polymorphism was analyzed using PCR and DNA Sequencing. In terms of binary genotypes and haplotypes, the 5/5-GC (p = 0.004), 6/7-GG (p = 0.02) and, 6/6-GG (p = 0.026) binary genotypes, and 5-C (p = 0.003), 7-G (p = 0.026) and 6-G (p = 0.025) haplotypes were differed significantly between the patients and the controls. This is the first study investigating the relationship between AD and MIF in terms of different genotypes, haplotypes and, alleles. The fact that the binary genotype and allele distributions are significantly different between the patient and control group, suggests that this MIF variants may play a role in the pathogenesis of AD.

摘要

阿尔茨海默病的特征是脑组织中存在淀粉样斑块和神经原纤维缠结，许多成分（例如急性期蛋白、细胞因子和蛋白酶）会导致疾病的进展，或者是病理过程的一部分。巨噬细胞迁移抑制因子（MIF）基因编码一种细胞因子，由淋巴细胞分泌，在类风湿性关节炎等自身免疫/炎症性疾病的发病机制中发挥作用。本研究的目的是探讨阿尔茨海默病与MIF基因启动子多态性之间的关联。对205名阿尔茨海默病（AD）患者和130名年龄性别匹配的健康个体进行MIF -173 G/C和MIF -794 CATT多态性研究。使用RT-PCR方法确定MIF -173 G/C的基因分型。使用 PCR 和 DNA 测序分析 MIF-794 CATT 多态性。就二元基因型和单倍型而言，5/5-GC ( p  = 0.004)、6/7-GG ( p  = 0.02) 和 6/6-GG ( p  = 0.026) 二元基因型和 5-C ( p  = 0.003)、7-G ( p  = 0.026) 和 6-G ( p  = 0.025) 单倍型在患者和对照组之间存在显着差异。这是第一项研究 AD 和 MIF 在不同基因型、单倍型和等位基因方面的关系。患者和对照组之间的二元基因型和等位基因分布显着不同，这一事实表明这种 MIF 变异可能在 AD 的发病机制中发挥作用。