Molecular Genetics of Sarcoidosis

Abstract

Sarcoidosis is a systemic inflammatory disorder characterised by the presence of noncaseating granulomas. The aetiology of sarcoidosis remains unknown. Although any organ system can be involved, the common cause of morbidity and mortality occurs from involvement of the lung, heart and nervous system. There has been extensive research, directed on the identification of candidate genes (both HLA and non‐HLA) that lead to dysregulation of the T‐cell response in sarcoidosis. However, most of these reported associations between these genes and susceptibility to sarcoidosis have not been replicated. Advances in genomics and proteomics, in concert with emerging technologies, are expected to provide further insight into pathogenesis and disease risk.

Key Concepts:

  • Sarcoidosis is a systemic inflammatory disorder characterised by the presence of noncaseating granulomas of unknown aetiology.

  • Studies have revealed many candidate genes (both HLA and non‐HLA) that lead to dysregulation of the T‐cell response in sarcoidosis.

  • A new strategy is to subgroup patients into distinct clinical phenotypes to help identify genes of importance for the disease.

  • Gene expression profiling in BAL fluid and blood performed at the time of presentation may help to better predict disease resolution or progression.

  • Advances in genomics and proteomics, in concert with emerging technologies, are expected to provide further insight into pathogenesis and disease risk.

Keywords: sarcoidosis; molecular genetics; candidate genes; sarcoidosis and HLA; cytokine genes and sarcoidosis; genome wide association studies and sarcoidosis

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Further Reading

Iannuzzi MC and Fontana JR (2011) Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA 305(4): 391–399.

Iannuzzi MC, Rybicki BA and Teirstein AS (2007) Sarcoidosis. New England Journal of Medicine 357(21): 2153–2165.

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Paul, Manju, and Iannuzzi, Michael(Jun 2012) Molecular Genetics of Sarcoidosis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021468]