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IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB

By Thorsten Thye, Edmund N. Browne, Margaret A. Chinbuah, John Gyapong, Ivy Osei, Ellis Owusu-Dabo, Norbert W. Brattig, Stefan Niemann, Sabine Rüsch-Gerdes, Rolf D. Horstmann and Christian G. Meyer

Abstract

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions −2849 , −1082 , −819 , and −592 and reconstructed the haplotypes. The IL10 low-producer haplotype −2849A/−1082A/−819C/−592C, compared to the high-producer haplotype −2849G/−1082G/−819C/−592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3–3.6) and PPD-positive controls (OR 2.09, CI 1.2–3.5). Lower IL-10 plasma levels in homozygous −2849A/−1082A/−819C/−592C carriers, compared to homozygous −2849G/−1082G/−819C/−592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2671601
Provided by: PubMed Central

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Citations

  1. (2008). ALOX5 variants associated with susceptibility to human pulmonary tuberculosis.
  2. (2006). An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults.
  3. (1997). An epidemic of tuberculosis with a high rate of tuberculin anergy among a population previously unexposed to tuberculosis, the Yanomami Indians of the Brazilian Amazon.
  4. (1997). An investigation of polymorphism in the interleukin-10 gene promoter.
  5. (2002). Antigenspecific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia.
  6. (2005). Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese.
  7. (2003). Association of the 22849 interleukin-10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis.
  8. (1999). CD4 T cell clones producing both interferongamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients.
  9. (2002). Ethnic-specific genetic associations with pulmonary tuberculosis.
  10. (2004). Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians.
  11. (2002). Frequency of functional interleukin-10 promoter polymorphism is different between relapse-onset and primary progressive multiple sclerosis.
  12. (2005). Genetic susceptibility to tuberculosis.
  13. (1999). Genomic control for association studies.
  14. (2007). Host genetics and susceptibility.
  15. (2003). Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis.
  16. (2003). Interindividual variations in constitutive interleukin-10 messenger RNA and protein levels and their association with genetic polymorphisms.
  17. (2004). Interleukin 10-2849AA genotype protects against pre-eclampsia.
  18. (2005). Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses.
  19. (1996). Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.
  20. (2004). Interleukin-10 promoter singlenucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy.
  21. (2000). Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells.
  22. (2004). Large-scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi.
  23. (2005). Med Common interleukin 10 polymorphism associated with decreased risk of tuberculosis.
  24. (2006). MycobacteriuM. tuberculosis drug resistance,
  25. (2006). No associations of human pulmonary tuberculosis with Sp110 variants.
  26. (2001). Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus.
  27. (2001). Optimizing human fertility and survival.
  28. (1993). Patterns of cytokine production by mycobacterium-reactive human T-cell clones.
  29. (1999). Polymorphic haplotypes of the interleukin-10 59 flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis.
  30. (2004). Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen.
  31. (2008). Pulmonary tuberculosis: Virulence of Mycobacterium africanum and relevance in HIV co-infection.
  32. (1990). Racial differences in susceptibility to infection by Mycobacterium tuberculosis.
  33. (2000). Regulation of IL-10 secretion after phagocytosis of MycobacteriuM. tuberculosis by human monocytic cells.
  34. (1990). Relative permissiveness of macrophages from black and white people for virulent tubercle bacilli.
  35. (1999). Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment.
  36. (2003). Serum cytokine concentrations do not parallel MycobacteriuM. tuberculosis-induced cytokine production in patients with tuberculosis.
  37. (1997). Simultaneous detection and strain differentiation of MycobacteriuM. tuberculosis for diagnosis and epidemiology.
  38. (1993). Strain identification of MycobacteriuM. tuberculosis by DNA fingerprinting: recommendations for a standardized methodology.
  39. (2004). The distribution of IL-10 promoter polymorphism in Thais.
  40. (2003). The dual role of IL-10.
  41. (1968). The epidemiology of tuberculosis infection in a closed environment.
  42. Topal-Sarıkaya A (2007) Interleukin-10 and Tumor Necrosis Factor-alpha Gene Polymorphisms in Tuberculosis. J Clin Immunol. Epub ahead of print.
  43. (1978). Tuberculosis in twins: a re-analysis of the Prophit survey.
  44. (1963). Tuberculosis in Twins.
  45. (1952). Tuberculosis, Man and Society. In: The White Plague.
  46. Westendorp RG (2006) Interleukin-10 promoter polymorphisms in male and female fertility and fecundity.

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