Association of MUC5B promoter polymorphism with interstitial lung disease in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis

Association of MUC5B promoter polymorphism with interstitial lung disease in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis




Abstract

       Interstitial lung disease (ILD) is a major complication and a prognostic factor of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).1 The prevalence of ILD is higher in Japanese AAV as compared with European populations.1 In a Japanese inception cohort study, 45.0% of patients with microscopic polyangiitis (MPA) were complicated by ILD.2 Such ethnic difference suggests a role for genetic background in the development of AAV-associated ILD (AAV-ILD). Single nucleotide polymorphism (SNP) rs35705950(G/T) in the promotor region of MUC5B, encoding mucin 5B, is a strong genetic factor for idiopathic pulmonary fibrosis (IPF). The risk allele T was associated with overexpression of mucin 5B in the lung.3 Recently, rs35705950 has been associated with rheumatoid arthritis-associated ILD (RA-ILD).4 Here, we examined whether rs35705950 is associated with AAV-ILD in case-control and case–case association studies. About 474 Japanese patients with AAV and 842 healthy Japanese controls were recruited at rheumatology or nephrology centres based on the clinical diagnosis of AAV, and classified according to the European Medicines Agency algorithm.5 The patients were examined for the presence or absence of ILD using CT or high-resolution CT (HRCT) by site investigators. 163 patients were reported positive and 264 negative for ILD (see online supplementary table S1,S2). This study was conducted in accordance with the Declaration of Helsinki.
 
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