A case-control study on the association of MIF -794 CATT5-8 and -173 G>C polymorphisms and its serum levels and the clinical severity of multiple sclerosis in Mexican patients

Abstract

Event Abstract Back to Event A case-control study on the association of MIF -794 CATT5-8 and -173 G>C polymorphisms and its serum levels and the clinical severity of multiple sclerosis in Mexican patients Victor A. Castaneda Moreno1, José F. Muñoz-Valle1*, Norma Torres Carrillo1, Oscar P. Gonzalez Perez1, 2, Miguel A. Macias Islas3, Jose L. Ruiz Sandoval4, Ofelia Padilla De La Torre3, Xochitl A. Trujillo Trujillo5 and Miguel Huerta Vieyra5 1 Universidad De Guadalajara, Mexico 2 Universidad de Colima, Mexico 3 Centro medico nacional de occidente, Neurologia Clinica, Mexico 4 Hospital Civil Fray Antonio Alcalde, Mexico 5 Universidad de Colima, Mexico The macrophage migration inhibitory factor (MIF), is one of the main cytokines involved in the tissular damage progression in several autoimmune diseases. This central role of MIF in inflammation and disease progression, suggest it might be a potential therapeutic target for multiple sclerosis (MS), however it is first necessary to know if it actually plays an important role on MS. We investigated whether the commonly occurring functional polymorphisms in the promoter of MIF have a significant impact on adults with MS in a Mexican Mestizo population. The patients for this study were recruited from the Centro Medico Nacional de Occidente, IMSS, in Guadalajara, Jalisco, Mexico, and the healthy subjects (HS) were recruited from the general population by invitation. A total of 200 patients and 200 HS were recruited from August 2013 to October 2014. Genotyping of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) polymorphisms was done through PCR and PCR-RFLP, respectively. MIF serum levels were determined by ELISA with a commercial kit provided by BioLegend. Statistical analysis was done with IBM’s SPSS v 20.0. Respect to the analysis of the serum levels of MIF there was significantly higher levels of MIF in MS patients (6.5 ng/ml) compared with HS (3.7 ng/ml) (p<0.01). We found a tendency to lower serum levels of MIF in patients that were on relapse (4.7 ng/ml) vs patients that were on remission (6.5 ng/ml), although this didn’t reach statistical significance (p=0.076). We also found a positive correlation (rs=0.267) between the serum levels of MIF on remission and the expanded disability status scale (EDSS) (p=0.009). On the analysis of the MIF polymorphisms genotypes and the clinical characteristics of MS patients, we found a significant association of the -173 GC genotype with a higher EDSS (p=0.027), as well as with a higher multiple sclerosis severity score (MSSS) (p=0.028). We also found an association of the -794 CATT 5/7 genotype with a higher MSSS (p<0.05). Finally, we found a significant association of the -794 CATT 5 allele with higher levels of MIF in serum of MS patients (carriers 7.59 ng/ml vs non carriers 5.35 ng/ml, p=0.026). In conclusion, elevated levels of MIF are associated with MS and seem to play a role in the disease progression as it rises in serum as increases EDSS. Also, the -794 CATT 5 allele is associated with higher MIF serum levels in MS, and the -794 CATT 5/7 genotype is associated with higher MSSS. Likewise, the -173 GC genotype is associated with higher EDSS and MSSS. However, further studies of other cytokines and their relationship with MIF are necessary to have a complete understanding of the role of this protein in MS. The present study was financed by the Consejo Nacional para la Ciencia y la Tecnología from Mexico, proyect number: 180663.