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Title: Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and-173 G>C): Association with MIF and TNFα in psoriatic arthritis
Author: Morales-Zambrano, R.
Bautista-Herrera, L.A.
De la Cruz-Mosso, U.
Villanueva-Quintero, G.D.
Padilla-Gutierrez, J.R.
Valle, Y.
Parra-Rojas, I.
Rangel-Villalobos, H.
Gutierrez-Urena, S.R.
Munoz-Valle, J.F.
Issue Date: 2014
Abstract: Psoriatic arthritis (PsA) is an autoimmune disease with a complex interaction of gene and with a dysregulation of pro-inflammatory cytokine such as Macrophage migration Inhibitory Factor (MIF) and Tumor Necrosis Factor-alpha (TNFα). Two polymorphisms identified in the promoter region of the MIF gene have been described: the STR-794 CATT5-8 (rs5844572) and the SNP-173 G>C (rs755622), which are associated with increased MIF levels in circulation and with autoimmune diseases in several populations. In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with PsA susceptibility and clinical variables as well as with MIF and TNFα serum levels in a Mexican-Mestizo population. Genotyping of the-794 CATT5-8 and-173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP respectively in 50 PsA patients and 100 healthy subjects (HS). MIF and TNFα serum levels were determined by ELISA. A significant increase of MIF (PsA: 7.8 vs. HS: 5.25 ng/mL; p < 0.001) and TNFα (PsA: 24.6 vs. HS: 9.9 pg/mL; p < 0.001) levels was found in PsA patients, a significant correlation was observed between MIF and TNFα (r = 0.41; p < 0.01). The 5,6 repeats genotype of the-794 CATT5-8 MIF was associated with protection to PsA (OR = 0.29; CI 0.77-0.98; p = 0.03), and the G/C genotype (OR = 7.5; CI 2.92-21.64; p < 0.001) and the-173*C allele (OR = 2.45; CI 1.43-4.20; p < 0.001) of the-173 G>C MIF were associated with susceptibility to PsA. In conclusion the-173*C allele is associated with susceptibility to PsA in Mexican-Mestizo population, whereas the correlation between MIF and TNFα soluble levels provided evidence that both cytokines are closely related in the pathophysiology of the PsA. © 2014, International Journal of Clinical and Experimental Medicine. All rights reserved.
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