TNF-alpha gene polymorphism: Clinical and biological implications

TNF-alpha is a proinflammatory cytokine that has been implicated in the sev erity of different immune-regulated diseases including autoimmune diseases and transplantation, The gene for TNF-alpha is located within the MHC regio n on chromosome 6p21.3. This is a highly polymorphic region, and the TNF-al pha itself contains a large number of polymorphisms. Some of these polymorp hisms form extended haplotypes with the HLA class I and II alleles. TNF pol ymorphisms have been investigated in different diseases and most often when ever there is an HLA association with the disease (for example IDDM and RA) association(s) with TNF polymorphisms has been described. There are many s tudies on the function of the TNF polymorphisms showing the influence of th e different alleles on the in vitro and in vivo levels of TNF production. H owever, recent studies in animal models suggest that not only polymorphisms within the TNF cluster are important in the regulation of TNF production b ut also the receptors as well (TNF R). This suggests that investigating pol ymorphisms within the TNF cluster and TNF receptors will be important in un derstanding the role of TNF regulation in a given disease. (C) 2000 Wiley-L iss. Inc.