Tumour necrosis factor-α single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies

Fiona Marriage, H. Chinoy, F. Salway, S. John, N. Fertig, B. D. Tait, C. V. Oddis, W. E R Ollier, R. G. Cooper

    Research output: Contribution to journalArticlepeer-review

    56 Downloads (Pure)

    Abstract

    Objective. To investigate haplotype tagging single nucleotide polymorphisms (SNPs) in the tumour necrosis factor α (TNF-α) gene, in UK Caucasian idiopathic inflammatory myopathy (IIM) patients. Methods. A cross-sectional, case-control study of four TNF-α SNPs was undertaken, comparing cases of polymyositis (PM) (n = 121), dermatomyositis (DM) (n = 109) and myositis overlapping with other connective tissue diseases (CTD-overlap) (n = 73) with normal subjects (n = 177). Subgroup analyses were undertaken after stratifying for myositis specific/associated antibodies. Results. The TNF-308A allele demonstrated a strong association with each myositis disease subgroup vs controls [PM, odds ratio (OR) 2.8, 95% confidence interval 1.9-4.3; DM, OR 2.5, 1.6-3.8; CTD-overlap, OR 3.3, 2.1-5.1]. The TNF-308GA/AA genotype frequency was significantly increased vs controls (PM, OR 3.7, 2.1-6.3; DM, OR 3.2, 1.8-5.5; CTD-overlap, OR 5.0, 2.6-9.6) suggesting a dominant model. The association was strongest in patients possessing anti-aminoacyl transfer RNA synthetase (anti-synthetase) (OR 5.1, 3.3-8.0) or -PM-Scl (OR 5.0, 2.7-8.9) antibodies. The -1031T allele was also a significant risk factor in DM (OR 2.2, 1.4-3.6), anti-synthetase (OR 2.9, 1.6-5.3) and -PM-Scl (OR 5.6, 1.9-6.4) antibody positive patients. The TNF-308A association was lost after adjusting for HLA-B*08, but remained independent of HLA-DQB1*02 (both are alleles forming part of the common ancestral haplotype). The HLA-B*08/TNF-308A/DRB1*03/ DQA1*05/DQB1*02 haplotype was a risk factor in all myositis subgroups vs controls (OR 3.0, 1.8-5.3). Conclusions. TNF-308A and -1031T alleles are significant risk factors in the IIMs. In the IIMs, the TNF-308A allele is part of the common ancestral haplotype, but is not independent of HLA-B*08. © 2007 The Author(s).
    Original languageEnglish
    Pages (from-to)1411-1416
    Number of pages5
    JournalRheumatology
    Volume46
    Issue number9
    DOIs
    Publication statusPublished - Sept 2007

    Keywords

    • Antibodies
    • Dermatomyositis
    • HLA, TNF-α
    • Myositis
    • Polymorphisms
    • Polymyositis

    Fingerprint

    Dive into the research topics of 'Tumour necrosis factor-α single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies'. Together they form a unique fingerprint.

    Cite this