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J Med Genet 50:290-297 doi:10.1136/jmedgenet-2013-101532
  • Complex traits

Recent advances in the genetics of sarcoidosis

  1. Johan Grunewald2
  1. 1Department of Medical and Surgical Sciences for Children and Adults, Center for Rare Lung Diseases, University of Modena and Reggio Emilia, Modena, Italy
  2. 2Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden
  1. Correspondence to Dr Paolo Spagnolo, Department of Medical and Surgical Sciences for Children and Adults, Center for Rare Lung Diseases, University Hospital, via del Pozzo 71, Modena 41124, Italy; paolo.spagnolo{at}unimore.it
  • Received 16 January 2013
  • Revised 18 February 2013
  • Accepted 25 February 2013
  • Published Online First 22 March 2013

Abstract

Sarcoidosis is a heterogeneous inflammatory disorder of unknown origin that may affect virtually any organ, although intrathoracic engagement is almost universal. Sarcoidosis may present rather dramatically as an acute disease, which usually resolves either spontaneously or with treatment, while other patients have an insidious onset and a chronic/progressive disease course. The different clinical phenotypes have led to the suggestion that sarcoidosis may consist of several separate entities. Yet, the characteristic immune response eventually leading to granuloma formation indicates that a number of features are common to all subgroups of the disease. Through a classical candidate gene approach, several genes of importance for sarcoidosis have been identified, and in some cases such gene variants associate with distinct clinical phenotypes. More recently, another approach to the search for sarcoidosis-associated genes has been applied, that is, through genome-wide association studies (GWAS). GWAS have led to the identification of a number of new genetic associations, although several of them need to be validated. Conversely, some of the previously identified human leucocyte antigen (HLA) associations with sarcoidosis have already been replicated in different cohorts and found to be quite strong, particularly in specific patient subgroups. In highly specialised centres such HLA associations already represent a useful aid in clinic practice for improving patient management. For the future, there is an urgent need for a better understanding, in particular, of gene–gene as well as gene–environmental interactions, both likely to be of importance for developing sarcoidosis.