SESSION TYPE: ILD - Bench to Bedside
PRESENTED ON: Wednesday, October 24, 2012 at 02:45 PM - 04:15 PM
PURPOSE: Interstitial lung disease (ILD) is common in patients with myositis but its pathogenesis is poorly understood. Identifying shared genetic risk factors could reveal pathobiologic overlap between myositis-related ILD and other forms of ILD. Familial interstitial pneumonia and sporadic idiopathic pulmonary fibrosis are associated with a specific single nucleotide polymorphism (SNP) in the promoter region of MUC5B (rs35705950). The association of this polymorphism with myositis-related ILD has not been described. We sought to determine the MUC5B minor allele frequency among ILD patients with and without associated myositis and the relationship between MUC5B variant expression and severity of illness at initial presentation.
METHODS: 129 participants with ILD were analyzed for a SNP (rs35705950) within the MUC5B promoter region using a TaqMan SNP genotyping assay. Sixty-seven had ILD without evidence of myositis (ILD); 62 had myositis-related ILD (myositis-ILD). A convenience sample of 27 patients with inclusion body myositis (IBM) without interstitial lung disease served as controls to establish the background minor allele frequency. The primary outcome measure was the MUC5B minor allele frequency in the two study populations (ILD vs. myositis-ILD). The secondary outcome measure was the difference in baseline mean forced vital capacity percent predicted (%FVC) between those with and without the MUC5B variant.
RESULTS: One hundred and nineteen patients (65 ILD, 54 myositis-ILD) were successfully genotyped. The MUC5B minor allele frequency was present in 28, 10, and 11% of the ILD, myositis-ILD, and IBM groups respectively (ILD vs. myositis-ILD p=0.004). The difference in baseline mean %FVC between those with and without the variant was 3.15% (95% CI [-4.49%, 10.78%]; p=0.415).
CONCLUSIONS: The MUC5B minor allele expression rate in non-myositis ILD is similar to published rates for patients with familial interstitial pneumonia and sporadic IPF. The MUC5B minor allele expression rate in myositis-ILD is consistent with published rates for control populations. MUC5B variant expression did not predict disease severity at initial presentation based on baseline %FVC.
CLINICAL IMPLICATIONS: The MUC5B promoter variant is not associated with the development of myositis-related ILD.
DISCLOSURE: The following authors have nothing to disclose: Cheilonda Johnson, Paul Rosen, Thomas Lloyd, John McGready, Maureen Horton, John Hall, Andrew Mammen, Sonye Danoff
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