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A systematic approach to the assessment of known TNF-α polymorphisms in Graves' disease

Genes & Immunity volume 5, pages 267–273 (2004)Cite this article

Abstract

Single-nucleotide polymorphisms (SNPs) within the tumour necrosis factor alpha (TNF-α) 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-α 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-α SNPs in a UK population and provides preliminary evidence for association of the TNF-α gene with GD.

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Acknowledgements

We acknowledge the Wellcome Trust and the special Trustees of the former United Birmingham Hospitals for their support. We thank J Carr-Smith, J Daykin, A Daly (University of Birmingham), M Armitage (Royal Bournemouth Hospital), A Hattersley (Royal Devon & Exeter Hospital), and PM Dodson (Birmingham Heartlands Hospital) for their help in recruiting patients for this study.

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Authors and Affiliations

  1. Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK

    M J Simmonds, J M Heward, H Foxall, J A Franklyn & S C L Gough

  2. JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Cambridge, UK

    J M M Howson

  3. Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK

    R Nithiyananthan & S C L Gough

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  1. M J Simmonds
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Correspondence to S C L Gough.

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Simmonds, M., Heward, J., Howson, J. et al. A systematic approach to the assessment of known TNF-α polymorphisms in Graves' disease. Genes Immun 5, 267–273 (2004). https://doi.org/10.1038/sj.gene.6364066

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