TUMOR-NECROSIS-FACTOR-ALPHA PROMOTER GENE POLYMORPHISM IN SARCOIDOSIS

Biallelic polymorphisms in the promoter region of the TNF-alpha gene ( TNFA) and in the first intron of the TNF-beta gene (TNFB) have been as sociated with variation in TNF-alpha production and with susceptibilit y to severe diseases, Among other functions, TNF-alpha plays a pivotal role in regulatory aspects of granuloma formation and sustenance, In sarcoidosis, a systemic granulomatous disorder of unknown aetiology, t he clinical course of the disease has been associated with the patient 's individual capacity of spontaneous TNF-alpha production by alveolar macrophages, We determined the TNFA and TNFB polymorphisms in 101 pat ients with pulmonary sarcoidosis and 216 healthy blood donors, A highl y significant shift to the more uncommon TNFA2 allele was found in the Lofgren syndrome patient group, which represents the acute form of th e disease with frequent spontaneous remission. The results show that g ene frequencies of the TNFA gene variation are significantly different within the clinical forms of sarcoidosis, indicating that genetic pre disposition for TNF-alpha production may play a role in the pathogenes is of the disease. (C) 1997 Academic Press Limited.