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 language | English (US) |
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Pages (from-to) | 219-224 |
Number of pages | 6 |
Journal | Journal of Rheumatology |
Volume | 32 |
Issue number | 2 |
State | Published - Feb 1 2005 |
Externally published | Yes |
Keywords
- Autoimmunity
- Rheumatoid arthritis
- Sjögren's syndrome
- Systemic lupus erythematosus
- Tuberculosis
- Tumor necrosis factor
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy
- Immunology