Influence of MUC5B gene on antisynthetase syndrome

Abstract

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.

Single Nucleotide Polymorphism in the IL17A Gene Is Associated with Interstitial Lung Disease Positive to Anti-Jo1 Antisynthetase Autoantibodies

“…Conversely, ANKRD55 SNP rs7731626 was a protective factor for DM/PM-ILD in the Chinese Han population [ 32 ]. Recently, López-Matías et al [ 33 ] studied a promoter polymorphism in MUC5B (rs35705950) in ASSD, a widely described gene associated with idiopathic pulmonary fibrosis (IPF) [ 34 ] and RA-ILD [ 35 ], two of the most critical ILDs. However, they did not find an association of rs35705950 with ASSD, suggesting a different pathogenic pathway between these diseases.…”

Interstitial pneumonia with autoimmune features (IPAF): A distinct group of idiopathic interstitial pneumonia - A case report on organizing pneumonia with positive anti Scl-70

“…Also, the MUC5B minor allele has been found to be overrepresented in them [16]. MUC5B codes for the protein called Mucin 5B, which is a major constituent of mucus in the respiratory tract [17]. Management needs to be carefully tailored to the patient because of the wide heterogeneity of IPAF.…”

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

“…A total of 168 unrelated Spanish patients of European ancestry diagnosed with ASSD (149 ASSD-ILD +) were enrolled in this cross-sectional study from the following Spanish hospitals: Hospital Universitario Marqués de Valdecilla (Santander), Hospital Clínico Universitario de Santiago (Santiago de Compostela), Hospital Universitario San Cecilio (Granada), Hospital Universitario Araba (Vitoria), Complejo Asistencial Universitario de León (León), Hospital Universitario Vall d´Hebron, Hospital Clínico de Barcelona and Hospital Universitario de Bellvitge (Barcelona), Hospital Universitario de la Princesa, Hospital Universitario La Paz, Hospital Universitario Fundación Jiménez Díaz, and Hospital General Universitario Gregorio Marañón (Madrid). As we originally defined 31 , 32 , these patients were recruited if they had an antisynthetase antibody positive in at least two determinations along with one or more findings of arthritis, myositis and/or ILD 2 – 4 , 33 . ILD was defined instrumentally by forced vital capacity (FVC) ≤ 80%, forced expiratory volume in one second/FVC ≥ 70%] and/or diffusing capacity of the lung for carbon monoxide (DLCO) < 80% and interstitial changes on chest high-resolution computed tomography 2 – 4 .…”