Illescas Oscar, Gomez-Verjan Juan C, García-Velázquez Lizbeth, Govezensky Tzipe, Rodriguez-Sosa Miriam
Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico.
División de Investigación Básica, Instituto Nacional de Geriatría, Mexico City, Mexico.
Front Genet. 2018 Mar 1;9:55. doi: 10.3389/fgene.2018.00055. eCollection 2018.
Human macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in several metabolic and inflammatory processes. Single nucleotide polymorphism (SNP) -173 G/C (rs755622) on gene has been associated with numerous diseases, such as arthritis and cancer. However, most of the reports concerning the association of MIF with these and other pathologies are inconsistent and remain quite controversial. Therefore, we performed a meta-analysis from 96 case-control studies on -173 G/C SNP and stratified the data according to the subjects geographic localization or the disease pathophysiology, in order to determine a more meaningful significance to this SNP. The polymorphism was strongly associated with an increased risk in autoimmune-inflammatory, infectious and age-related diseases on the dominant (OR: 0.74 [0.58-0.93], < 0.01; OR: 0.81 [0.74-0.89], < 0.0001; and OR: 0.81 [0.76-0.87], < 0.0001, respectively) and the recessive models (OR: 0.74 [0.57-0.095], < 0.01; OR: 0.66 [0.48-0.92], < 0.0154; and OR: 0.70 [0.60-0.82], < 0.0001, respectively). Also, significant association was found in the geographic localization setting for Asia, Europe and Latin America subdivisions in the dominant (OR: 0.76 [0.69-0.84], < 0.0001; OR: 0.77 [0.72-0.83], < 0.0001; OR: 0.61 [0.44-0.83], -value: 0.0017, respectively) and overdominant models (OR: 0.85 [0.77-0.94], < 0.0001; OR: 0.80 [0.75-0.86], < 0.0001; OR: 0.73 [0.63-0.85], -value: 0.0017, respectively). Afterwards, we implemented a network meta-analysis to compare the association of the polymorphism for two different subdivisions. We found a stronger association for autoimmune than for age-related or autoimmune-inflammatory diseases, and stronger association for infectious than for autoimmune-inflammatory diseases. We report for the first time a meta-analysis of rs755622 polymorphism with a variety of stratified diseases and populations. The study reveals a strong association of the polymorphism with autoimmune and infectious diseases. These results may help direct future research on -173 G/C in diseases in which the relation is clearer and thus assist the search for more plausible applications.
人类巨噬细胞移动抑制因子（MIF）是一种细胞因子，在多种代谢和炎症过程中发挥作用。基因上的单核苷酸多态性（SNP）-173 G/C（rs755622）与许多疾病相关，如关节炎和癌症。然而，大多数关于MIF与这些及其他病症关联的报告并不一致，仍存在很大争议。因此，我们对96项关于-173 G/C SNP的病例对照研究进行了荟萃分析，并根据受试者的地理定位或疾病病理生理学对数据进行分层，以确定该SNP更有意义的显著性。该多态性在显性模型（分别为：比值比[OR]：0.74[0.58 - 0.93]，P<0.01；OR：0.81[0.74 - 0.89]，P<0.0001；以及OR：0.81[0.76 - 0.87]，P<0.0001）和隐性模型（分别为：OR：0.74[0.57 - 0.95]，P<0.01；OR：0.66[0.48 - 0.92]，P<0.0154；以及OR：0.70[0.60 - 0.82]，P<0.0001）中与自身免疫性炎症、感染性和年龄相关疾病风险增加密切相关。此外，在亚洲、欧洲和拉丁美洲细分地区的地理定位分析中，在显性模型（分别为：OR：0.76[0.69 - 0.84]，P<0.0001；OR：0.77[0.72 - 0.83]，P<0.0001；OR：0.61[0.44 - 0.83]，P值：0.0017）和超显性模型（分别为：OR：0.85[0.77 - 0.94]，P<0.0001；OR：0.80[0.75 - 0.86]，P<0.0001；OR：0.73[0.63 - 0.85]，P值：0.0017）中也发现了显著关联。之后，我们进行了网状荟萃分析，以比较该多态性在两个不同细分群体中的关联情况。我们发现，该多态性与自身免疫性疾病的关联强于与年龄相关或自身免疫性炎症疾病的关联，与感染性疾病的关联强于与自身免疫性炎症疾病的关联。我们首次报告了rs755622多态性与多种分层疾病和人群的荟萃分析。该研究揭示了该多态性与自身免疫性和感染性疾病的密切关联。这些结果可能有助于指导未来在关系更明确的疾病中对-173 G/C的研究，从而有助于寻找更合理的应用。
