Autoimmunity and tuberculosis. Opposite association with TNF polymorphism

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

Resultado de la investigación: Contribución a RevistaArtículo

123 Citas (Scopus)

Resumen

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.
Idioma originalEnglish (US)
Páginas (desde-hasta)219-224
Número de páginas6
PublicaciónJournal of Rheumatology
DOI
EstadoPublished - feb 2005

Huella dactilar

Autoimmunity
Tuberculosis
Tumor Necrosis Factor-alpha
Sjogren's Syndrome
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Genes
Autoimmune Diseases
Single Nucleotide Polymorphism
Alleles
Immunogenetics
Genetic Selection
Heterozygote
Restriction Fragment Length Polymorphisms
Haplotypes
Odds Ratio
Genotype
Polymerase Chain Reaction
DNA

Citar esto

Correa, Paula A. ; Gomez, Luis M. ; Cadena, Jose ; Anaya, Juan Manuel. / Autoimmunity and tuberculosis. Opposite association with TNF polymorphism. En: Journal of Rheumatology. 2005 ; pp. 219-224.
@article{cdb2d509f1dc45a690003dee1eaec558,
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). 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.",
author = "Correa, {Paula A.} and Gomez, {Luis M.} and Jose Cadena and Anaya, {Juan Manuel}",
year = "2005",
month = "2",
doi = "0315162X-32-219 [pii]",
language = "English (US)",
pages = "219--224",
journal = "Journal of Rheumatology",
issn = "0315-162X",
publisher = "Journal of Rheumatology",

}

Autoimmunity and tuberculosis. Opposite association with TNF polymorphism. / Correa, Paula A.; Gomez, Luis M.; Cadena, Jose; Anaya, Juan Manuel.

En: Journal of Rheumatology, 02.2005, p. 219-224.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Autoimmunity and tuberculosis. Opposite association with TNF polymorphism

AU - Correa, Paula A.

AU - Gomez, Luis M.

AU - Cadena, Jose

AU - Anaya, Juan Manuel

PY - 2005/2

Y1 - 2005/2

N2 - 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.

AB - 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.

U2 - 0315162X-32-219 [pii]

DO - 0315162X-32-219 [pii]

M3 - Article

C2 - 15693080

SP - 219

EP - 224

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

ER -