Genetic association study of NF-κB genes in UK Caucasian adult and juvenile onset idiopathic inflammatory myopathy

Hector Chinoy, Charles K-C Li, Hazel Platt, Noreen Fertig, Hemlata Varsani, Harsha Gunawardena, Zoe Betteridge, Chester V Oddis, Neil J McHugh, Lucy R Wedderburn, William E R Ollier, Robert G Cooper, UK Adult Onset Myositis Immunogenetic Consortium and UK Juvenile Dermatomyositis Research Group

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective. Treatment-resistant muscle wasting is an increasingly recognized problem in idiopathic inflammatory myopathy (IIM). TNF-α is thought to induce muscle catabolism via activation of nuclear factor-kappa B (NF-κB). Several genes share homology with the NF-κB family of proteins. This study investigated the role of NF-κB-related genes in disease susceptibility in UK Caucasian IIM.

Methods. Data from 362 IIM cases [274 adults, 49 (±14.0) years, 72% female; 88 juveniles, 6 (±3.6) years, 73% female) were compared with 307 randomly selected Caucasian controls. DNA was genotyped for 63 single nucleotide polymorphisms (SNPs) from NF-κB-related genes. Data were stratified by IIM subgroup/serotype.

Results. A significant allele association was observed in the overall IIM group vs controls for the IKBL-62T allele (rs2071592, odds ratio 1.5, 95% CI 1.21, 1.89, corrected P = 0.0086), which strengthened after stratification by anti-Jo-1 or -PM-Scl antibodies. Genotype analysis revealed an increase for the AT genotype in cases under a dominant model. No other SNP was associated in the overall IIM group. Strong pairwise linkage disequilibrium was noted between IKBL-62T, TNF-308A and HLA-B*08 (D′ = 1). Using multivariate regression, the IKBL-62T IIM association was lost after adjustment for TNF-308A or HLA-B*08.

Conclusion. An association was noted between IKBL-62T and IIM, with increased risk noted in anti-Jo-1- and -PM-Scl antibody-positive patients. However, the IKBL-62T association is dependent on TNF-308A and HLA-B*08, due to strong shared linkage disequilibrium between these alleles. After adjustment of the 8.1 HLA haplotype, NF-κB genes therefore do not independently confer susceptibility in IIM.
Original languageEnglish
Pages (from-to)794-799
Number of pages6
JournalRheumatology
Volume51
Issue number5
DOIs
Publication statusPublished - May 2012

Fingerprint Dive into the research topics of 'Genetic association study of NF-κB genes in UK Caucasian adult and juvenile onset idiopathic inflammatory myopathy'. Together they form a unique fingerprint.

  • Cite this

    Chinoy, H., Li, C. K-C., Platt, H., Fertig, N., Varsani, H., Gunawardena, H., Betteridge, Z., Oddis, C. V., McHugh, N. J., Wedderburn, L. R., Ollier, W. E. R., Cooper, R. G., & UK Adult Onset Myositis Immunogenetic Consortium and UK Juvenile Dermatomyositis Research Group (2012). Genetic association study of NF-κB genes in UK Caucasian adult and juvenile onset idiopathic inflammatory myopathy. Rheumatology, 51(5), 794-799. https://doi.org/10.1093/rheumatology/ker379