title: A systematic approach to the assessment of known TNF-alpha polymorphisms in Graves' disease.
abstract: Single-nucleotide polymorphisms (SNPs) within the tumour necrosis factor alpha (TNF-alpha) gene on chromosome 6p21.3 have been associated with many autoimmune diseases; however, results have been conflicting and accurate allele frequencies have never been established in a UK Caucasian population. The aim of this study was to assess the frequency of 22 known TNF-alpha SNPs in a UK Caucasian control population and investigate association of all polymorphisms with >5% minor allele frequency in a large case-control data set of patients with Graves' disease (GD). Eight of the 22 SNPs had minor allele frequencies >5% and were investigated further. The other 14 SNPs were present in the UK population at frequencies ranging from 0 to 4.7%. A significant increase of the A allele of the -238 SNP was seen in GD patients when compared with control subjects (9.6 vs 6.8%, respectively; P=0.003) and mirrored in the genotype distribution (P=0.009). Furthermore, association of the -238 SNP appears not to be due to linkage disequilibrium of the known HLA-DRB1(*)03 associations with GD. This study has established accurate allele frequencies of TNF-alpha SNPs in a UK population and provides preliminary evidence for association of the TNF-alpha gene with GD.
authors.affiliation: Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Simmonds
authors.forename: J M
authors.initials: JM
authors.lastname: Heward
authors.forename: J M M
authors.initials: JM
authors.lastname: Howson
authors.forename: H
authors.initials: H
authors.lastname: Foxall
authors.forename: R
authors.initials: R
authors.lastname: Nithiyananthan
authors.forename: J A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: S C L
authors.initials: SC
authors.lastname: Gough
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha