MIF-173G/C (rs755622) Polymorphism as Risk Factor for Acute Lymphoblastic Leukemia Development in Children

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.