From U Colorado: The Pulmonary Fibrosis-Associated MUC5B Promoter Polymorphism does not Influence the Development of Interstitial Pneumonia in Systemic Sclerosis

http://www.ncbi.nlm.nih.gov/pubmed/22576636

Chest. 2012 May 10. [Epub ahead of print]

The Pulmonary Fibrosis-Associated MUC5B Promoter Polymorphism does not Influence the Development of Interstitial Pneumonia in Systemic Sclerosis.

Peljto AL, Steele MP, Fingerlin TE, Hinchcliff ME, Murphy E, Podlusky S, Carns M, Schwarz M, Varga J, Schwartz DA.

Source

1 University of Colorado Denver, School of Public Health, Aurora, CO.

Abstract

ABSTRACT

INTRODUCTION:

Over 80% of patients with systemic sclerosis (SSc) develop lung involvement, most commonly interstitial pneumonia (IP). We recently identified a common variant in the promoter region of MUC5B (rs35705950) that has a significant effect on the risk of developing both familial and sporadic forms of IP. We hypothesized that this MUC5B promoter polymorphism is also associated with IP in subjects with SSc.

METHODS:

We examined the minor allele frequency of the MUC5B polymorphism among 231 subjects with SSc, 109 with IP and 122 without IP. IP diagnosis was confirmed by HRCT imaging and defined as presence of reticular infiltrates and/or honeycomb cysts. Forced vital capacity (FVC) and diffusing capacity (DLCO) were also assessed.

RESULTS:

We found no association between IP and the MUC5B polymorphism among SSc subjects (OR=1.2, p-value=0.80). The frequencies of the MUC5B polymorphism among SSc subjects with IP (10.6%) and without IP (9.4%) were similar to the frequency observed in a population of unaffected controls (9.0%). In secondary analyses, we found the MUC5B polymorphism was not significantly associated with either FVC (p-value=0.42) or DLCO (p-value=0.06). No association with SSc-associated IP was found even when we used a more conservative definition of IP (FVC≤70% and evidence of reticulations or honeycombing vs. SSc FVC>70% and no evidence of reticulation or honeycombing).

CONCLUSION:

While SSc-associated IP is clinically, radiologically, and histologically similar to other forms of IP, it appears to have distinct genetic risk factors. This study highlights the genetic and phenotypic heterogeneity of IP in general.