title: Tumor necrosis factor-alpha -308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans.
abstract: The aim of this study was to determine the frequency and potential relevance of the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy controls (99 were typed for HLA-DR). We observed an increased frequency of HLA-DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF polymorphism analysis showed a significant increased frequency of TNF -238 GG genotype in the whole group of RA patients when compared to healthy controls (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and non-severe RA patients, the increased frequency of -238 GG genotype only was observed in patients with non-severe forms of the disease. Analysis of -308 polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated with susceptibility to develop severe RA in Mexicans. This association could be independent from HLA-DR alleles and might be used as a prognostic marker for severe RA.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico.
authors.forename: Alma Angelica
authors.initials: AA
authors.lastname: Rodríguez-Carreón
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zúñiga
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Hernández-Pacheco
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rodríguez-Pérez
authors.forename: Nonanzit
authors.initials: N
authors.lastname: Pérez-Hernández
authors.forename: Jose Vicente
authors.initials: JV
authors.lastname: Montes de Oca
authors.forename: Mario H
authors.initials: MH
authors.lastname: Cardiel
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha