TNF-alpha gene polymorphism: clinical and biological implications.

TNF-alpha is a proinflammatory cytokine that has been implicated in the severity of different immune-regulated diseases including autoimmune diseases and transplantation. The gene for TNF-alpha is located within the MHC region on chromosome 6p21.3. This is a highly polymorphic region, and the TNF-alpha itself contains a large number of polymorphisms. Some of these polymorphisms form extended haplotypes with the HLA class I and II alleles. TNF polymorphisms have been investigated in different diseases and most often whenever there is an HLA association with the disease (for example IDDM and RA) association(s) with TNF polymorphisms has been described. There are many studies on the function of the TNF polymorphisms showing the influence of the different alleles on the in vitro and in vivo levels of TNF production. However, recent studies in animal models suggest that not only polymorphisms within the TNF cluster are important in the regulation of TNF production but also the receptors as well (TNF R). This suggests that investigating polymorphisms within the TNF cluster and TNF receptors will be important in understanding the role of TNF regulation in a given disease. Copyright 2000 Wiley-Liss, Inc.