Department of Biochemistry, Faculty of Sciences, Damietta University, New Damietta, Egypt.
Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
J Gene Med. 2018 Sep;20(9):e3044. doi: 10.1002/jgm.3044. Epub 2018 Aug 2.
Macrophage inhibitory factor (MIF) is a pro-inflammatory cytokine modulating monocyte motility and a pleiotropic regulator of different biological and cellular processes. The MIF-173G/C (rs755622) polymorphism is found in the promoter region and affects its activity. The present study investigated the MIF polymorphism as a risk factor for the development of acute lymphoblastic leukemia (ALL) in Egyptian children.
We analyzed the MIF-173G/C (rs755622) polymorphism in 180 ALL cases and 150 healthy control children by amplification of the gene using a polymerase chain reaction followed by restriction endonuclease digestion and running on an agarose gel for visualization of the product.
We found a significant incidence of the homozygous polymorphic (CC) genotype and the combined polymorphic genotypes (GC + CC) in ALL patients compared to healthy controls (p = 0.001 and p = 0.007, respectively), whereas the wild-type genotype (GG) was more common in healthy controls (p = 0.006). Multivariate logistic regression analysis adjustment for MIF different genotypes and other potential risk factors such as age, sex and parental smoking indicated that the CC genotype is the only significant risk factor for the test (p = 0.02). We also noted that, by increasing the C-allele representation within the gene [GC, CC], there was an increase in total leukocytic count (p = 0.09 and p = 0.001, respectively) that may reflect the bad prognostic impact of the polymorphic allele, although further studies are needed.
The results of the present study indicate that the MIF-173G/C (rs755622) polymorphism is a risk factor for childhood ALL development with respect to both homozygous and combined polymorphic genotypes. In addition, the increased leukocytic count in synchronization with the increased representation of the polymorphic C-allele may reflect its bad prognostic impact.
巨噬细胞抑制因子（MIF）是一种促炎细胞因子，调节单核细胞的运动，是多种生物学和细胞过程的多效调节剂。MIF-173G/C（rs755622）多态性位于启动子区域，影响其活性。本研究探讨了 MIF 多态性作为埃及儿童急性淋巴细胞白血病（ALL）发病的危险因素。
我们通过聚合酶链反应扩增基因，然后用限制性内切酶消化，在琼脂糖凝胶上电泳，以可视化产物，分析了 180 例 ALL 病例和 150 例健康对照儿童的 MIF-173G/C（rs755622）多态性。
与健康对照组相比，ALL 患者中纯合多态性（CC）基因型和组合多态性基因型（GC+CC）的发生率显著升高（p=0.001 和 p=0.007），而野生型基因型（GG）在健康对照组中更为常见（p=0.006）。多变量 logistic 回归分析调整 MIF 不同基因型和其他潜在危险因素（如年龄、性别和父母吸烟）后，CC 基因型是唯一有意义的危险因素（p=0.02）。我们还注意到，随着基因内 C 等位基因表达增加[GC，CC]，白细胞总数增加（p=0.09 和 p=0.001），这可能反映了多态性等位基因的不良预后影响，但需要进一步研究。
本研究结果表明，MIF-173G/C（rs755622）多态性是儿童 ALL 发病的危险因素，无论是纯合多态性还是组合多态性基因型。此外，与多态性 C 等位基因表达增加相吻合的白细胞计数增加可能反映了其不良预后影响。
