Background Risk alleles at genome loci containing interferon induced with helicase C domain 1 (IFIH1) and human leukocyte antigen (HLA) genes closely associated with dermatomyositis (DM) in European population [1–3]. Autoantibody targeted to melanoma differentiation associated protein 5 (MDA5), a protein encoded by IFIH1, was associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality in DM .
Objectives To estimate the associations between HLA and IFIH1 rs1990760 polymorphisms and susceptibility to DM and anti-MDA5 antibody expression in Chinese population.
Methods HLA-DRB1and IFIH1 rs1990760 polymorphisms were determined in 102 DM patients and 400 healthy controls. Anti-MDA5 antibodies and ILD were evaluated by ELISA and high-resolution computed tomography (HRCT), respectively.
Results Frequencies of HLA-DRB1*04:01 were significantly higher in DM (4.41% vs 0.63%, OR 7.34, 95%CI 2.84–18.95, P 0.00004, Pc 0.001), but the frequency of HLA-DRB1*14 (0.98% vs 5.88%, OR 0.16, 95%CI 0.05–0.55, P 0.004, Pc 0.049) was significantly lower than that of healthy controls. Compared with the healthy controls, HLA-DRB1*04:01 was associated with the development of ILD in DM (7.14% vs 0.63%, OR 12.23, 95%CI 4.97–30.10, P 5.03×10–8, Pc 1.81×10–6). The frequency of HLA-DRB1*09 (5.36% vs 18.48%, OR 0.25, 95%CI 0.10–0.63, P 0.003, Pc 0.042) was significantly lower in DM patients with ILD than in DM patients without ILD, suggesting it is a protective allele for ILD in DM. The frequencies of HLA-DRB1*04:01 (8.51% vs 0.63%, OR 14.79, 95%CI 6.17–35.45, P 1.53×10-9, Pc 5.49×10–8) and HLA-DRB1*12:02 (21.28% vs 10.00%, OR 2.43, 95%CI 1.43–4.14, P 0.001, Pc 0.037) were significantly increased in anti-MDA5 positives than in controls. Compared with anti-MDA5 negatives, the frequency of HLA-DRB1*12:02 (21.28% vs 4.55%, OR 5.68, 95% CI 2.22–14.48, P 0.0003, Pc 0.010) were significantly increased in anti-MDA5 positives. No association was observed between the IFIH1 rs1990760 and DM, anti-MDA5 antibody expression and ILD status.
Conclusions HLA-DRB1 alleles, but not IFIH1 polymorphisms, may be associated with the susceptibility to DM, ILD involvement and anti-MDA5 expression in Chinese population.
Gono T, Kawaguchi Y, Sugiura T, et al. Interferon-induced helicase (IFIH1) polymorphism with systemic lupus erythematosus and dermatomyositis/polymyositis[J]. Modern rheumatology, 2010, 20(5): 466–470.
O'Hanlon T P, Rider L G, Mamyrova G, et al. HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies[J]. Arthritis & Rheumatism, 2006, 54(11): 3670–3681.
Betteridge Z E, Gunawardena H, Chinoy H, et al. Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis[J]. Annals of the rheumatic diseases, 2009, 68(10): 1621–1625.
Chen Z, Cao M, Plana M N, et al. Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease: a review of the literature and a meta-analysis[J]. Arthritis care & research, 2013, 65(8): 1316–1324.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.