The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome

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Abstract

Background

Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ, TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS).

Methods

A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ, TNF-α and IL-10 for their associations with SARS.

Results

IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner ( P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility.

Conclusion

IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility.

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Most cited references 21

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Coronavirus as a possible cause of severe acute respiratory syndrome.

V Cheng, A. Yung, J. S. Malik Peiris … (2003)

An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

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Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones

MW Bond, DF Fiorentino, TR Mosmann (1989)

A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.

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Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.

A Wilson, J A Symons, T McDowell … (1997)

Tumor necrosis factor alpha (TNF alpha) is a potent immunomodulator and proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. For example, plasma levels of TNF alpha are positively correlated with severity and mortality in malaria and leishmaniasis. We have previously described a polymorphism at -308 in the TNF alpha promoter and shown that the rare allele, TNF2, lies on the extended haplotype HLA-A1-B8-DR3-DQ2, which is associated with autoimmunity and high TNF alpha production. Homozygosity for TNF2 carries a sevenfold increased risk of death from cerebral malaria. Here we demonstrate, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line. Footprint analysis using DNase I and B cell nuclear extract showed the generation of a hypersensitive site at -308 and an adjacent area of protection. There was no difference in affinity of the DNA-binding protein(s) between the two alleles. These results show that this polymorphism has direct effects on TNF alpha gene regulation and may be responsible for the association of TNF2 with high TNF alpha phenotype and more severe disease in infections such as malaria and leishmaniasis.

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Author and article information

Journal

Journal ID (nlm-ta): BMC Infect Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date Collection: 2006

Publication date (Electronic): 4 May 2006

Volume: 6

Page: 82

Affiliations

[1 ]Department of Paediatrics and Adolescent Medicine, The Hong Kong Jockey Club Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

[2 ]Department of Pathology, Pamela Nethersole Youde Hospital, Hong Kong SAR, China

[3 ]Department of Pathology, United Christian Hospital, Hong Kong SAR, China

[4 ]Princess Margaret Hospital, Hong Kong SAR, China

[5 ]Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China

[6 ]Government Virus Unit, Department of Health, Hong Kong SAR, China

[7 ]Department of Microbiology, The Hong Kong Jockey Club Research Centre, Pokfulam, The University of Hong Kong, Hong Kong SAR, China

Article

Publisher ID: 1471-2334-6-82

DOI: 10.1186/1471-2334-6-82

PMC ID: 1468415

PubMed ID: 16672072

SO-VID: cd988d0e-8c4f-469c-88e8-dd328116d782

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome

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Abstract

Background

Methods

Results

Conclusion

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European Respiratory Society: COVID-19

Most cited references 21

Coronavirus as a possible cause of severe acute respiratory syndrome.

Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones

Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.

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