Solo Metadatos

Autoimmunity and tuberculosis. Opposite association with TNF polymorphism.

Título de la revista
Anaya, Juan-Manuel
Correa, Paula A.
Gomez, Luis M.
Cadena, Jose




ISSN de la revista
Título del volumen
Instituto Nacional de Salud


Métricas alternativas

Objective. To examine the influence of the –308 and –238 single nucleotide polymorphisms (SNP) of tumor necrosis factor-? 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.
Palabras clave
Tumor Necrosis Factor , Rheumatoid Arthritis , Tuberculosis , Systemic Lupus Erythematosus , Sjögren’s Syndrome , Autoimmunity