02145nas a2200277   4500000000100000008004100001260001300042653002400055653002500079653002600104653003800130653001100168653003600179653003000215653002700245100001500272700002000287700001600307245005400323856006200377300001100439490000600450050001600456520138100472022001401853       2004                            d  c2004 Aug10aAutoimmune Diseases10aCase-Control Studies10aCommunicable Diseases10aGenetic Predisposition to Disease10aHumans10aPolymorphism, Single Nucleotide10aPromoter Regions, Genetic10aTumor Necrosis Factors1 aBayley J-P1 aOttenhoff T H M1 aVerweij C L00aIs there a future for TNF promoter polymorphisms?  uhttp://www.nature.com/gene/journal/v5/n5/pdf/6364055a.pdf  a315-290 v5  aBAYLEY 20043 a<p>The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied -308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.</p>  a1466-4879