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.
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Disclosure of Interest None declared