title: Autoimmunity and tuberculosis. Opposite association with TNF polymorphism.
abstract: OBJECTIVE
  To examine the influence of the -308 and -238 single nucleotide polymorphisms (SNP) of tumor necrosis factor-a gene (TNF) on patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjogren's syndrome (SS), and tuberculosis (TB).
  
  
  METHODS
  Genomic DNA from patients with RA (n = 165), SLE (n = 100), primary SS (n = 67), and TB (n = 135) and ethnically matched controls (n = 430) was genotyped for TNF -308 and -238 SNP by PCR-RFLP.
  
  
  RESULTS
  TNF -308A allele was associated with RA (odds ratio, OR 1.8, p = 0.002), SLE (OR 2.6, p < 0.0001), and primary SS (OR 2.9, p < 0.0001). TNF -308G was associated with TB (OR 1.8, p = 0.02). The -308 GG genotype was protective for autoimmunity (p < 0.003). TNF -238A allele was protective for autoimmunity but represented a susceptibility factor for TB (OR 2.2, p < 0.0001). Haplotype -308A-238G was a protective factor against TB, whereas it carried susceptibility for RA, SLE, and primary SS (p < 0.0001).
  
  
  CONCLUSIONS
  The results show an opposite association of TNF polymorphism with autoimmunity and TB, and suggest the existence of heterozygote advantage, sustaining the hypothesis that autoimmune diseases are a consequence of natural selection for enhanced TB resistance. Data also provide genetic evidence supporting the common variants/multiple disease hypothesis, which emphasizes that many disease genes may not be disease-specific, and that similar immunogenetic mechanisms underlie autoimmune diseases.
authors.affiliation: Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Correa
authors.forename: Luis M
authors.initials: LM
authors.lastname: Gomez
authors.forename: Jose
authors.initials: J
authors.lastname: Cadena
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004247:DNA