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Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers
  1. Samuel Y Ash1,
  2. Rola Harmouche2,
  3. Rachel K Putman1,
  4. James C Ross2,
  5. Fernando J Martinez3,
  6. Augustine M Choi3,
  7. Russell P Bowler4,
  8. Elizabeth A Regan5,
  9. Jeffrey L Curtis6,7,
  10. MeiLan K Han6,
  11. Richard C Boucher8,
  12. Wanda K O’Neal8,
  13. Hiroto Hatabu9,
  14. David A Lynch10,
  15. Ivan O Rosas1,
  16. Gary M Hunninghake1,
  17. Raul San Jose Estepar2,
  18. George R Washko1
  19. the COPDGene Investigators
  1. 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  2. 2Department of Radiology, Laboratory of Mathematics in Imaging, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  3. 3Department of Medicine, Weil Cornell Medical College, New York, USA
  4. 4Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, USA
  5. 5Department of Medicine, Division of Rheumatology, National Jewish Health, Denver, Colorado, USA
  6. 6Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA
  7. 7Department of Internal Medicine, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
  8. 8Department of Medicine, Marisco Lung Institute, University of North Carolina, Chapel Hill, North Carolina, USA
  9. 9Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  10. 10Department of Radiology, National Jewish Health, Denver, Colorado, USA
  1. Correspondence to Dr Samuel Y Ash, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA; syash{at}bwh.harvard.edu

Abstract

A single-nucleotide polymorphism (rs35705950) in the mucin 5B (MUC5B) gene promoter is associated with pulmonary fibrosis and interstitial features on chest CT but may also have beneficial effects. In non-Hispanic whites in the COPDGene cohort with interstitial features (n=454), the MUC5B promoter polymorphism was associated with a 61% lower odds of a prospectively reported acute respiratory disease event (P=0.001), a longer time-to-first event (HR=0.57; P=0.006) and 40% fewer events (P=0.016). The MUC5B promoter polymorphism may have a beneficial effect on the risk of acute respiratory disease events in smokers with interstitial CT features.

  • copd exacerbations
  • interstitial fibrosis
  • idiopathic pulmonary fibrosis

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Footnotes

  • Contributors The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. SYA, RH, RSJE and GRW designed the study and wrote the initial manuscript. SYA performed the statistical analyses. RH, JCR and RSJE wrote the feature detection algorithm. All authors contributed to the production of the final of the manuscript.

  • Funding This work was supported by NHLBI R01 HL089897 and R01 HL089856. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens and Sunovion. Additional funding for this work includes: National Institutes of Health grants: T32-HL007633 (SYA and RKP), R01-HL107246 (RH, RSJE and GRW), R01-HL116933 (RH, RSJE and GRW), R01-HL111024 (GMH), P01-HL114501 (GRW) and R01-HL089856 (RSJE and GRW); VA Merit Review I01 CX000911 (JLC) as well as Boehringer-Ingelheim Pharmaceuticals (GRW) and Pulmonary Fibrosis Foundation IM Rosenzweig Junior Investigator Award (SYA). Drs SYA, RH, RKP and RSJE report no other relevant disclosures. Dr GMH reports consulting for Medna LLC and Gerson Lehrman Group and has served on a scientific advisory boards for Genentech and Boehringer-Ingelheim. Dr GRW reports other support from Genentech, GlaxoSmithKline, PulmonX, and Janssen. This study was funded by Boehringer Ingelheim.

  • Disclaimer Funding for this work included grants from The National Institutes of Health and Boehringer Ingelheim Pharmaceuticals Inc (BIPI). BIPI had no role in the design, analysis or interpretation of the results in this study. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to BIPI substances, as well as intellectual property considerations.

  • Competing interests SYA, RH, RKP and RSJE report no other relevant disclosures. GMH reports consulting for Medna LLC, and Gerson Lehrman Group, and has served on a scientific advisory boards for Genentech and Boehringer-Ingelheim. GRW reports other support from Genentech, GlaxoSmithKline, PulmonX, and Janssen.

  • Ethics approval The following Institutional Review Boards (IRB) approved the COPDGene study: Partners IRB, Ann Arbor VA Research IRB, Baylor University IRB, Columbia University Medical Center IRB, Duke University Health System IRB, Health Partners IRB, Johns Hopkins Medicine IRB, Harbor UCLA Medical Center IRB, Michael E DeBakey VA Medical Center IRB, Minneapolis VA Health Care System IRB, Morehouse School of Medicine IRB, National Jewish Health IRB, Temple University IRB, University of Alabama IRB, University of California San Diego Human Research Protections Program, University of Iowa IRB, University of Michigan Medical School IRB, University of Minnesota IRB, University of Pittsburgh IRB, Office of the IRB University of Texas Health Science Center San Antonio.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data from the COPDGene Study are made available centrally by the data coordinating center.

  • Collaborators The COPDGene Investigators: James D. Crapo MD, Edwin K. Silverman MD PhD, Barry J. Make MD, Elizabeth A. Regan MD PhD, Jeffrey L. Curtis MD, Carlos H. Martinez MD MPH, Lisa McCloskey BBA RRT, Perry G. Pernicano MD, Nicola A. Hanania MD MS, Philip Alapat MD, Mustafa Atik MD CCRP, Venkata Bandi MD, Laura Bertrand RN RPFT, Aladin Boriek PhD, Kalpalatha Guntupalli MD, Elizabeth Guy MD, Veronica V. Lenge de Rosen MD, Amit D. Parulekar MD, Dawn L. DeMeo MD MPH, Lystra P. Hayden MD, Craig P. Hersh MD MPH, Brian D. Hobbs MD, Aimee Garciano, Cherie Maguire B.S., Francine L. Jacobson MD MPH, George R. Washko MD, R. Graham Barr MD DrPH, Casandra Almonte, John H.M. Austin MD, Belinda M. D’Souza MD, Gregory D.N. Pearson MD, Michael Sheffey, Byron Thomashow MD, Neil MacIntyre, Jr. MD, Linda Brown, H. Page McAdams MD, Lacey Washington MD, Robert A. Wise MD, Ferdouse Begum PhD, Robert Brown MD, Cheryl Clare, Teresa Concordia, Marie Daniel RN CCRP, Nadia N. Hansel MD MPH, Karen Horton MD, Meredith McCormack MD MHS, Nirupama Putcha MD MHS, Meagan Scott, Richard Casaburi PhD MD, Alessandra Adami PhD, Matt Budoff MD, Robert Cao, Deborah Cavanaugh, Leticia Diaz, Hans Fischer MD PhD, Renee Love Indelicato, Dong Li MD PhD, Carmen Lopez-Garcia, Janos Porszasz MD PhD, Harry B. Rossiter PhD, William Stringer MD, Miriam Urrutia, Chris H. Wendt MD, Brian Bell MD, Miranda Deconcini, Ken Kunisaki MD MS, Charlene McEvoy MD MPH, Joseph H. Tashjian MD, Natalie Woodruff BS RRT, Marilyn G. Foreman MD MS, Eugene A. Berkowitz MD PhD, Steven Fair, Eric L. Flenaugh MD, Gloria Westney MD MS, Russell P. Bowler MD PhD, Debra Dyer MD, Jay Finigan MD, Andrew Hull, David A. Lynch MB, Jason Varasteh, Richard Rosiello MD, Kathy Allain, Mary Charpentier, Diane Kirk RN, Anne McDonald, David Pace MD, Gerard J. Criner MD, David Ciccolella MD, Francis Cordova MD, Chandra Dass MD, Gilbert D’Alonzo DO, Parag Desai MD, Dee Fehrle BSN MHA, Carla Grabianowski RN BSN, Michael Jacobs PharmD, Gayle M. Jones RN BSN CCRP, Steven Kelsen MD PhD, Victor Kim MDA. James Mamary MD, Nathaniel Marchetti DO, Aditi Satti MD, Kartik Shenoy MD, Robert Steiner MD, Alex Swift MD, Maria Vega-Sanchez MD, Mark T. Dransfield MD, Erica Anderson, William C. Bailey MD, Surya P. Bhatt MD, Stephanie Ford, Anand Iyer MD, Merry-Lynn McDonald PhD, Hrudaya Nath MD, Gabriela Oates PhD, Sushil K. Sonavane MD, Mike Wells MD, Elizabeth Westfall MPH, Joe W. Ramsdell MD, Dagni Chuki, Tarek El Hajjaoui, Katie Kinninger RCP CCRC, Karl Perez, Xavier Soler MD PhD, Andrew Yen MD, Alejandro Comellas MD, Kaylene Crawford, Angie Delsing, Spyridon Fortis MD, Fozia Ghafoor, Janet Keating, Cassandra Kennedy, John D. Newell Jr. MD, Debra O’Connell-Moore, Phyllis Pirotte, Amna Rizvi-Toner, Thomas Sardone, Kim Sprenger RN BS, Marlee Wallace, MeiLan K. Han MD MS, Gretchen Bautista, Craig J. Galban PhD, Mary Kay Hamby BS RRT RPFT, Ella Kazerooni MD Wassim Labaki MD, Fernando Martinez MD, Joanne Billings MD MPH, Tadashi L. Allen MD, Abbie Begnaud MD, Nate Gaeckle MD, Mary P. Lynch RRT, Frank Sciurba MD, Jessica Bon MD, Mary J. Bryner BS RRT RPFT, Divay Chandra MD MSc, Paula Consolaro CCRC, Carl R. Fuhrman MD, Rhonda Lincoln, Lizzie Stempkowski, Patricia A. Tomko BS RRT, Antonio Anzueto MD, Sandra G. Adams MD, Diego Maselli-Caceres MD, Karl McCloskey, Mario E. Ruiz MD, Harjinder Singh MD

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