title: Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Association with messenger RNA expression and sTNF-alpha.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor alpha (TNFalpha). We investigated the relationship of TNFalpha-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFalpha (sTNFalpha) in 50 RA and 100 healthy subjects (HS).
  
  
  METHODS
  Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFalpha-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFalpha was quantified by real-time polymerase chain reaction. The sTNFalpha levels were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The TNFalpha-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS (P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS (P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFalpha-238 polymorphism. Rheumatoid arthritis patients showed high TNFalpha mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFalpha levels in both TNFalpha polymorphisms. The correlation of sTNFalpha levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed.
  
  
  CONCLUSIONS
  The TNFalpha-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFalpha expression.
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Edith
authors.initials: E
authors.lastname: Oregón-Romero
authors.forename: Mónica
authors.initials: M
authors.lastname: Vázquez-Del Mercado
authors.forename: Sandra Luz
authors.initials: SL
authors.lastname: Ruiz-Quezada
authors.forename: Rosa Elena
authors.initials: RE
authors.lastname: Navarro-Hernández
authors.forename: Héctor
authors.initials: H
authors.lastname: Rangel-Villalobos
authors.forename: Gloria
authors.initials: G
authors.lastname: Martínez-Bonilla
authors.forename: Ana Guilaisne
authors.initials: AG
authors.lastname: Bernard-Medina
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Bañuelos
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha