MIF functional polymorphisms (-794 CATT5-8 and-173 G > C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population
MIF functional polymorphisms (-794 CATT5-8 and-173 G > C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population
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DOI：
10.1016/j.jneuroim.2018.04.006
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发表时间：
2018-07-15
影响因子：
3.3
通讯作者：
Munoz-Valle, J. F.
中科院分区：
文献类型：
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作者：
Castaneda-Moreno, V. A.;De la Cruz-Mosso, U.;Munoz-Valle, J. F.
巨噬细胞移动抑制因子（Macrophage migration inhibitor factor，MIF）是一种与多种自身免疫性疾病如系统性红斑狼疮、类风湿性关节炎和银屑病关节炎的组织损伤相关的细胞因子。MIF在多发性硬化症（MS）中的作用及其多态性的贡献在我们的人群中尚不清楚。因此，我们决定在墨西哥西部人群中研究-794 CATT（5-8）（rs 5844572）和-173 G > C（rs755622）MIF多态性与MS、临床变量和MIF血清水平的遗传关联。采用PCR和PCR-RFLP方法对230例符合McDonald诊断标准的MS患者和248例正常对照进行基因分型，并采用ELISA试剂盒检测血清MIF水平。分别通过EDSS和MSSS评分评估MS的严重程度和进展。携带-794 CATT（5-8）MIF多态性的5个重复等位基因的基因型与无携带者相比，其血清MIF水平更高，且5，7杂合基因型的存在有助于MS患者疾病严重程度的增加和损害进展。值得注意的是，当我们按性别分层时，发现两种MIF多态性的风险等位基因（7个重复和-173*C）对男性的EDSS和MSSS评分有影响（p < 0.01）。这项研究表明，MIF多态性的多态性等位基因可以作为性别特异性疾病修饰剂，增加男性墨西哥-梅斯蒂索西部人口的MS的严重程度和进展。
Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT(5-8 )(rs5844572) and -173 G > C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT(5-8)MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.