Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsSeibold, Max A
Wise, Anastasia L
Speer, Marcy C
Steele, Mark P
Brown, Kevin K
Loyd, James E
Fingerlin, Tasha E
Groshong, Steve D
Evans, Christopher M
Adler, Kenneth B
Dickey, Burton F
du Bois, Roland M
Yang, Ivana V
Talbert, Janet L
Crews, Anne L
Slifer, Susan H
Roy, Michelle G
Hennessy, Corinne E
Schwarz, Marvin I
Schwartz, David A
MetadataShow full item record
CitationN. Engl. J. Med. 2011, 364 (16):1503-12
AbstractBACKGROUND: The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk. METHODS: Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 3.4-Mb region of chromosome 11p15 in 82 families. We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls. MUC5B expression was assessed in lung tissue. RESULTS: Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes. The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P=1.2×10(-15); allelic association with idiopathic pulmonary fibrosis, P=2.5×10(-37)). The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 6.8 (95% confidence interval [CI], 3.9 to 12.0) and 20.8 (95% CI, 3.8 to 113.7), respectively, for familial interstitial pneumonia and 9.0 (95% CI, 6.2 to 13.1) and 21.8 (95% CI, 5.1 to 93.5), respectively, for idiopathic pulmonary fibrosis. MUC5B expression in the lung was 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0.001). The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 37.4 times as high as in unaffected subjects homozygous for the wild-type allele, P<0.001). MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis. CONCLUSIONS: A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis. Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis. (Funded by the National Heart, Lung, and Blood Institute and others.).
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
RightsArchived with thanks to The New England journal of medicine
- Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis.
- Authors: Johnson C, Rosen P, Lloyd T, Horton M, Christopher-Stine L, Oddis CV, Mammen AL, Danoff SK
- Issue date: 2017 Sep
- MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.
- Authors: Juge PA, Lee JS, Ebstein E, Furukawa H, Dobrinskikh E, Gazal S, Kannengiesser C, Ottaviani S, Oka S, Tohma S, Tsuchiya N, Rojas-Serrano J, González-Pérez MI, Mejía M, Buendía-Roldán I, Falfán-Valencia R, Ambrocio-Ortiz E, Manali E, Papiris SA, Karageorgas T, Boumpas D, Antoniou K, van Moorsel CHM, van der Vis J, de Man YA, Grutters JC, Wang Y, Borie R, Wemeau-Stervinou L, Wallaert B, Flipo RM, Nunes H, Valeyre D, Saidenberg-Kermanac'h N, Boissier MC, Marchand-Adam S, Frazier A, Richette P, Allanore Y, Sibilia J, Dromer C, Richez C, Schaeverbeke T, Lioté H, Thabut G, Nathan N, Amselem S, Soubrier M, Cottin V, Clément A, Deane K, Walts AD, Fingerlin T, Fischer A, Ryu JH, Matteson EL, Niewold TB, Assayag D, Gross A, Wolters P, Schwarz MI, Holers M, Solomon JJ, Doyle T, Rosas IO, Blauwendraat C, Nalls MA, Debray MP, Boileau C, Crestani B, Schwartz DA, Dieudé P
- Issue date: 2018 Dec 6
- Effect of Muc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias.
- Authors: van der Vis JJ, Snetselaar R, Kazemier KM, ten Klooster L, Grutters JC, van Moorsel CH
- Issue date: 2016 May
- Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis.
- Authors: Hobbs BD, Putman RK, Araki T, Nishino M, Gudmundsson G, Gudnason V, Eiriksdottir G, Zilhao Nogueira NR, Dupuis J, Xu H, O'Connor GT, Manichaikul A, Nguyen J, Podolanczuk AJ, Madahar P, Rotter JI, Lederer DJ, Barr RG, Rich SS, Ampleford EJ, Ortega VE, Peters SP, O'Neal WK, Newell JD Jr, Bleecker ER, Meyers DA, Allen RJ, Oldham JM, Ma SF, Noth I, Jenkins RG, Maher TM, Hubbard RB, Wain LV, Fingerlin TE, Schwartz DA, Washko GR, Rosas IO, Silverman EK, Hatabu H, Cho MH, Hunninghake GM
- Issue date: 2019 Dec 1
- The pulmonary fibrosis-associated MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis.
- Authors: Peljto AL, Steele MP, Fingerlin TE, Hinchcliff ME, Murphy E, Podlusky S, Carns M, Schwarz M, Varga J, Schwartz DA
- Issue date: 2012 Dec