title: The pulmonary fibrosis-associated MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis.
abstract: BACKGROUND
  More than 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 the presence of reticular infiltrates and/or honeycomb cysts. FVC and diffusing capacity of the lung for carbon monoxide (Dlco) were also assessed.
  
  
  RESULTS
  We found no association between IP and the MUC5B polymorphism among subjects with SSc (OR = 1.1, P = .80). The frequencies of the MUC5B polymorphism among subjects with SSc with IP (10.6%) and without IP (9.4%) were similar to the frequency observed in a population of unaffected control subjects (9.0%). In secondary analyses, we found the MUC5B polymorphism was not significantly associated with either FVC (P = .42) or Dlco (P = .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 &gt; 70% and no evidence of reticulation or honeycombing).
  
  
  CONCLUSIONS
  Although 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.
authors.affiliation: School of Public Health, University of Colorado Denver, Aurora, CO. Electronic address: anna.peljto@ucdenver.edu.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Peljto
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Steele
authors.affiliation: School of Public Health, University of Colorado Denver, Aurora, CO.
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Monique E
authors.initials: ME
authors.lastname: Hinchcliff
authors.affiliation: School of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Elissa
authors.initials: E
authors.lastname: Murphy
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Sofia
authors.initials: S
authors.lastname: Podlusky
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Mary
authors.initials: M
authors.lastname: Carns
authors.affiliation: School of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Marvin
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: John
authors.initials: J
authors.lastname: Varga
authors.affiliation: School of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D002248:Carbon Monoxide / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics*; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000150:complications*; D014057:Tomography, X-Ray Computed; D014797:Vital Capacity / Q000502:physiology
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B; D002248:Carbon Monoxide