SAT0007 Genetic Polymorphisms of HLA-DRB1 Are Associated with Dermatomyositis and ANTI-MDA5 Antibodies in Chinese
Authors: Y. Wang, Z. Chen, L. Sun
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> 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 <sup>[1–3]</sup>. 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 <sup>[4]</sup>. <h3>Objectives</h3> To estimate the associations between HLA and IFIH1 rs1990760 polymorphisms and susceptibility to DM and anti-MDA5 antibody expression in Chinese population. <h3>Methods</h3> 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. <h3>Results</h3> Frequencies of HLA-DRB1*04:01 were significantly higher in DM (4.41% <i>vs</i> 0.63%, OR 7.34, 95%CI 2.84–18.95, <i>P</i> 0.00004, <i>Pc</i> 0.001), but the frequency of HLA-DRB1*14 (0.98% <i>vs</i> 5.88%, OR 0.16, 95%CI 0.05–0.55, <i>P</i> 0.004, <i>Pc</i> 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% <i>vs</i> 0.63%, OR 12.23, 95%CI 4.97–30.10, <i>P</i> 5.03×10<sup>–8</sup>, <i>Pc</i> 1.81×10<sup>–6</sup>). The frequency of HLA-DRB1*09 (5.36% <i>vs</i> 18.48%, OR 0.25, 95%CI 0.10–0.63, <i>P</i> 0.003, <i>Pc</i> 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% <i>vs</i> 0.63%, OR 14.79, 95%CI 6.17–35.45, <i>P</i> 1.53×10<sup>-9</sup>, <i>Pc</i> 5.49×10<sup>–8</sup>) and HLA-DRB1*12:02 (21.28% <i>vs</i> 10.00%, OR 2.43, 95%CI 1.43–4.14, <i>P</i> 0.001, <i>Pc</i> 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% <i>vs</i> 4.55%, OR 5.68, 95% CI 2.22–14.48, <i>P</i> 0.0003, <i>Pc</i> 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. <h3>Conclusions</h3> HLA-DRB1 alleles, but not IFIH1 polymorphisms, may be associated with the susceptibility to DM, ILD involvement and anti-MDA5 expression in Chinese population. <h3>References</h3> 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. O9Hanlon 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 &amp; 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 &amp; research, 2013, 65(8): 1316–1324. <h3>Disclosure of Interest</h3> None declared