title: Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis.
abstract: BACKGROUND
  A polymorphism (rs35705950) 3 kb upstream of MUC5B, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population.
  
  
  METHODS
  Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis.
  
  
  RESULTS
  A significant association of the MUC5B promoter single nucleotide polymorphism with IPF (p=2.04 × 10(-17); OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The MUC5B variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF.
  
  
  CONCLUSIONS
  We confirm the MUC5B variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.
authors: Interstitial Lung Disease Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK. c.stock@imperial.ac.uk
authors: Carmel J
authors: CJ
authors: Stock
authors: Hiroe
authors: H
authors: Sato
authors: Carmen
authors: C
authors: Fonseca
authors: Winston A S
authors: WA
authors: Banya
authors: Philip L
authors: PL
authors: Molyneaux
authors: Huzaifa
authors: H
authors: Adamali
authors: Anne-Marie
authors: AM
authors: Russell
authors: Christopher P
authors: CP
authors: Denton
authors: David J
authors: DJ
authors: Abraham
authors: David M
authors: DM
authors: Hansell
authors: Andrew G
authors: AG
authors: Nicholson
authors: Toby M
authors: TM
authors: Maher
authors: Athol U
authors: AU
authors: Wells
authors: Gisela E
authors: GE
authors: Lindahl
authors: Elisabetta A
authors: EA
authors: Renzoni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011658:Pulmonary Fibrosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D012507:Sarcoidosis / Q000150:complications / Q000235:genetics; D012595:Scleroderma, Systemic / Q000150:complications* / Q000235:genetics; D014797:Vital Capacity / Q000235:genetics*; D055815:Young Adult
chemical_list: D055257:Mucin-5B