title: Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter.
abstract: We have identified three new human tumor necrosis factor-alpha (TNF-alpha) promoter polymorphisms with single nucleotide (nt) substitutions at -862, -856, and -574 nt relative to the TNF-alpha transcription start site. The -862 and -856 nt TNF-alpha promoter polymorphisms occur with high frequency in Caucasian and Cambodian individuals and are each non-randomly associated with three extended HLA haplotypes. This study, in which 61 independent TNF-alpha promoters were analyzed spanning from -977 to +93 nt relative to the TNF-alpha mRNA cap site, establishes a new canonical TNF-alpha promoter sequence. Furthermore, we show that none of the three novel polymorphisms at -862, -856 and -574 nt or polymorphisms previously described at positions -238, -308 and +70 have an effect upon TNF-alpha gene expression in activated lymphocytes. Thus, these TNF-alpha promoter polymorphisms likely serve as markers for neighboring genes encoding HLA or other undefined molecules in the MHC that may influence disease susceptibility.
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Uglialoro
authors.forename: D
authors.initials: D
authors.lastname: Turbay
authors.forename: P A
authors.initials: PA
authors.lastname: Pesavento
authors.forename: J C
authors.initials: JC
authors.lastname: Delgado
authors.forename: F E
authors.initials: FE
authors.lastname: McKenzie
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.forename: D
authors.initials: D
authors.lastname: Hartl
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
authors.forename: A E
authors.initials: AE
authors.lastname: Goldfeld
mesh_terms: D000818:Animals; D001483:Base Sequence; D002160:Cambodia; D002460:Cell Line; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha