Autoimmunity and tuberculosis. Opposite association with TNF polymorphism

Paula A. Correa, Luis M. Gomez, Jose Cadena, Juan Manuel Anaya

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123 Scopus citations

Abstract

Objective. To examine the influence of the -308 and -238 single nucleotide polymorphisms (SNP) of tumor necrosis factor-α gene (TNF) on patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren'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). Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalJournal of Rheumatology
Volume32
Issue number2
StatePublished - Feb 1 2005
Externally publishedYes

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Keywords

  • Autoimmunity
  • Rheumatoid arthritis
  • Sjögren's syndrome
  • Systemic lupus erythematosus
  • Tuberculosis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Correa, P. A., Gomez, L. M., Cadena, J., & Anaya, J. M. (2005). Autoimmunity and tuberculosis. Opposite association with TNF polymorphism. Journal of Rheumatology, 32(2), 219-224.