| dc.description | Cytokine unbalance is responsible for the pathogenesis of diverse inflammatory, autoimmune and infectious diseases, and Tumor Necrosis Factor Alpha (TNFalpha), among other cytokines, plays a central role. TNFalpha production can be regulated at the transcriptional, post-transcriptional, and translational levels. Variability in the promoter and coding regions of the TNFalpha gene may modulate the magnitude of its secretory response. Up to date, several single nucleotide polymorphisms (SNPs) have been identified in the human TNFalpha gene promoter. One of these, is a guanine to adenine transition at position -308, that generates the TNF1 and TNF2 alleles, respectively. The TNF2 allele is associated to a high in vitro TNF expression, and it has also been linked to an increased susceptibility and severity, for a variety of illnesses, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer disease and cerebral malaria among others. It is also associated with a higher septic shock susceptibility and mortality. The investigation of polymorphisms within the TNFalpha cluster will be important in understanding the role of TNFalpha regulation in specific diseases (Rev Méd Chile 2002; 130: 1043-50). | |
