title: Tumor necrosis factor alpha-308 gene variants in relation to major histocompatibility complex alleles and Felty's syndrome.
abstract: The location of the human TNF genes within the MHC complex has prompted much speculation about the role of TNF alleles in the etiology of MHC-associated autoimmune diseases. On sequencing the 5' regulatory region of the human TNFA gene a G (TNFA-308G) to A (TNFA-308A) transition polymorphism at position -308 was discovered. We have developed a simple PCR assay to facilitate the screening of the -308 polymorphism at the DNA level. In view of the possible linkage between the TNFA-308A allele and a certain MHC type, TNFA-308 genotypes in HLA-typed healthy individuals (n = 88) were determined. A statistically significant association between the TNFA-308A allele and HLA-DR3, DQB1*0201, DQA1*0501, A1, B8, and the NcoI 5.5-kb RFLP of the TNFB gene was observed. In addition, we determined the frequency of the TNFA-308A allele in patients with FS (n = 13), an HLA-DR4-associated disease. In this study, no association was found of Felty's syndrome with the TNFA-308A allele, indicating that this allele does not appear to be a susceptibility factor for FS.
authors.affiliation: Department of Rheumatology, Leiden University Hospital, The Netherlands.
authors.forename: B M
authors.initials: BM
authors.lastname: Brinkman
authors.forename: M J
authors.initials: MJ
authors.lastname: Giphart
authors.forename: A
authors.initials: A
authors.lastname: Verhoef
authors.forename: E L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: A M
authors.initials: AM
authors.lastname: Naipal
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: C L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005258:Felty Syndrome / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha