Tumour 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 associated with variation in TNF-alpha production and with susceptibility 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, the 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 patients with pulmonary sarcoidosis and 216 healthy blood donors. A highly significant shift to the more uncommon TNFA2 allele was found in the Löfgren syndrome patient group, which represents the acute form of the disease with frequent spontaneous remission. The results show that gene frequencies of the TNFA gene variation are significantly different within the clinical forms of sarcoidosis, indicating that genetic predisposition for TNF-alpha production may play a role in the pathogenesis of the disease.