Autoimmunity and tuberculosis. Opposite association with TNF polymorphism

• Published in: Journal of rheumatology 2005-02, Vol.32 (2), p.219-224
• Main Authors: CORREA, PAULA A, GOMEZ, LUIS M, CADENA, JOSE, ANAYA, JUAN-MANUEL
• Format: Article
• Language: English
• Subjects: Adult; Bacterial diseases; Biological and medical sciences; Diseases of the osteoarticular system; DNA - genetics; Female; Genetic Predisposition to Disease; Genotype; Human bacterial diseases; Humans; Infectious diseases; Inflammatory joint diseases; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - pathology; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sjogren's Syndrome - genetics; Sjogren's Syndrome - pathology; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - pathology; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0315-162X; 1499-2752

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). 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.