Genetic aspects in sarcoidosis

Sarcoidosis is an immune-mediated, multiorgan, granulomatous disorder thoug ht to be triggered by an intricate combination of environmental and genetic factors. Two robust lines of evidence support the hypothesis of a genetic component in the pathogenesis of sarcoidosis: racial variation in its epide miology and familial clustering of cases. The relationship between epidemio logy and environmental factors affecting variations in sarcoidosis incidenc e/prevalence and presentation are reviewed, as well as strategies to be pur sued in the search for susceptibility genes for the disorder. Pathogenic processes leading to sarcoid granuloma formation and maintenance have prompted investigators interested in the genetics of sarcoidosis to f ocus mainly on major histocompatibility complex genes, and indeed a remarka ble amount of data has been accumulated during the last two decades. Whilst in contrast with some autoimmune disorders a clear association between hum an leukocyte antigen (HLA) and sarcoidosis is still a controversial issue, there is, however, a general agreement that some HLA genes are related to p henotypic variations of the disease. Some genetic investigators have focuse d on T-cell receptor genes, immunoglobulin genes, angiotensin converting en zyme gene, chemokine genes and others. From a review of studies performed in different racial and ethnic groups, a reasonable suggestion arises that genetic factors are the major determinan t in the racial variations in the epidemiology of the disorder. This assump tion is, however, so far Limited by lack of studies considering bath geneti c and environmental factors simultaneously.