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Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?

Genes & Immunity volume 4, pages 533–540 (2003)Cite this article

Abstract

Patients with meningococcal disease have increased plasma levels of proinflammatory cytokines IL-6, IL-1β, and TNF-α, with higher levels associated with fatal outcome. This study investigated whether polymorphisms in genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and IL-1Ra, are associated with the outcome in patients with meningococcal disease. Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389 controls. The IL-6 −174 G/G and IL-10 −1082 A/A genotypes were more frequent in nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL-10). An association was also found between meningococcal disease and the IL-1RN VNTR polymorphism, but no association was observed with the LTA +252, TNF −308, IL-10 −592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in meningococcal disease.

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Acknowledgements

We thank Dr K Butler for clinical data collection and advice on designing a severity scoring system; Sandra Morgan, Lisa Shiels, Anne McDaid, and Jennifer Malone for secretarial assistance; Michelle Ni Luanaigh and Karen Murphy for sample collection.

Author information

Authors and Affiliations

  1. Department of Genetics, Trinity College, Dublin, Ireland

    J Balding, W J Livingstone & L Mynett-Johnson

  2. Department of Paediatrics, The Children's University Hospital, Dublin, Ireland

    C M Healy

  3. Department of Paediatrics, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland

    C M Healy & O P Smith

  4. National Centre for Hereditary Coagulation Disorders, St James' Hospital, Dublin, Ireland

    B White

  5. Irish Meningococcal and Meningitis Reference Laboratory, The Children's University Hospital, Dublin, Ireland

    M Cafferkey

  6. Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland

    M Cafferkey

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  1. J Balding
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  2. C M Healy
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  3. W J Livingstone
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  7. O P Smith
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Correspondence to O P Smith.

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Ethical approval: The study was approved by the Ethics Committee of the Children's University Hospital, Temple Street, Dublin.

Financial support: This project was funded by a grant from Novo Nordisk, Denmark.

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Balding, J., Healy, C., Livingstone, W. et al. Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?. Genes Immun 4, 533–540 (2003). https://doi.org/10.1038/sj.gene.6364020

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