title: Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and -173 G>C): association with MIF and TNFα in psoriatic arthritis.
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.
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México ; Doctorado en Ciencias Biomédicas (Inmunología), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: Ramsés
authors.initials: R
authors.lastname: Morales-Zambrano
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Bautista-Herrera
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México ; Doctorado en Ciencias Biomédicas (Inmunología), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: Ulises
authors.initials: U
authors.lastname: De la Cruz-Mosso
authors.affiliation: Instituto Dermatológico de Jalisco "Dr. José Barba Rubio", Secretaría de Salud Jalisco Guadalajara, Jalisco, México.
authors.forename: Guadalupe D
authors.initials: GD
authors.lastname: Villanueva-Quintero
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Padilla-Gutiérrez
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: Yeminia
authors.initials: Y
authors.lastname: Valle
authors.affiliation: Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero Chilpancingo, Guerrero, México.
authors.forename: Isela
authors.initials: I
authors.lastname: Parra-Rojas
authors.affiliation: Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: Héctor
authors.initials: H
authors.lastname: Rangel-Villalobos
authors.affiliation: Servicio de Reumatología, O.P.D. Hospital Civil de Guadalajara "Fray Antonio Alcalde" Guadalajara, Jalisco, México.
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Gutiérrez-Ureña
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara Guadalajara, Jalisco, México.
authors.forename: José F
authors.initials: JF
authors.lastname: Muñoz-Valle
keywords: Macrophage migration inhibitory factor; polymorphism; psoriatic arthritis; tumor necrosis factor alpha