Journal article
MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study
Thorax, Vol.78(6), pp.566-573
05/16/2023
DOI: 10.1136/thorax-2021-218139
PMCID: PMC9899287
PMID: 36690926
Abstract
Background The MUC5B promoter variant (rs35705950) and telomere length are linked to pulmonary fibrosis and CT-based qualitative assessments of interstitial abnormalities, but their associations with longitudinal quantitative changes of the lung interstitium among community-dwelling adults are unknown. Methods We used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1-6 (2000-2018)) and MUC5B genotype (n=4552) and telomere length (n=4488) assessments. HAA was defined as the per cent of imaged lung with attenuation of -600 to -250 Hounsfield units. We used linear mixed-effects models to examine associations of MUC5B risk allele (T) and telomere length with longitudinal changes in HAAs. Joint models were used to examine associations of longitudinal changes in HAAs with death and interstitial lung disease (ILD). Results The MUC5B risk allele (T) was associated with an absolute change in HAAs of 2.60% (95% CI 0.36% to 4.86%) per 10 years overall. This association was stronger among those with a telomere length below an age-adjusted percentile of 5% (p value for interaction=0.008). A 1% increase in HAAs per year was associated with 7% increase in mortality risk (rate ratio (RR)=1.07, 95% CI 1.02 to 1.12) for overall death and 34% increase in ILD (RR=1.34, 95% CI 1.20 to 1.50). Longer baseline telomere length was cross-sectionally associated with less HAAs from baseline scans, but not with longitudinal changes in HAAs. Conclusions Longitudinal increases in HAAs were associated with the MUC5B risk allele and a higher risk of death and ILD.
Details
- Title: Subtitle
- MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study
- Creators
- John S. Kim - University of VirginiaAni W. Manichaikul - University of VirginiaEric A. Hoffman - University of IowaPallavi Balte - Columbia UniversityMichaela R. Anderson - Columbia UniversityElana J. Bernstein - Columbia UniversityPurnema Madahar - Columbia UniversityElizabeth C. Oelsner - Columbia UniversitySteven M. Kawut - University of PennsylvaniaArtur Wysoczanski - Columbia UniversityAndrew F. Laine - Columbia UniversityAyodeji Adegunsoye - University of ChicagoJennie Z. Ma - University of VirginiaMargaret A. Taub - Johns Hopkins UniversityRasika A. Mathias - Johns Hopkins UniversityStephen S. Rich - University of VirginiaJerome Rotter - Harbor–UCLA Medical CenterImre Noth - University of VirginiaChristine Kim Garcia - Columbia UniversityR. Graham Barr - Columbia UniversityAnna J. Podolanczuk - Weill Cornell Medicine
- Resource Type
- Journal article
- Publication Details
- Thorax, Vol.78(6), pp.566-573
- DOI
- 10.1136/thorax-2021-218139
- PMID
- 36690926
- PMCID
- PMC9899287
- NLM abbreviation
- Thorax
- ISSN
- 0040-6376
- eISSN
- 1468-3296
- Publisher
- Bmj Publishing Group
- Number of pages
- 8
- Grant note
- K23-HL-150301 / Pulmonary Fibrosis Foundation Scholars Award from the National Heart, Lung and Blood Institute (NHLBI) DK063491 / National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) R01HL-120393; U01HL-120393; HHSN268201800001I / TOPMed Data Coordinating Center NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 3R01HL-117626-02S1; HHSN268201800002I / TOPMed Informatics Research Center R01-HL131565; R01-HL077612; R01-HL093081; RC1-HL100543; R01-HL-103676; R01-HL105756 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) UL1TR001881 / National Center for Advancing Translational Sciences, CTSI 3U54HG003067-13S1 / Broad Institute of MIT and Harvard K23-AR-075112 / National Institute of Arthritis and Musculoskeletal and Skin Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
- Language
- English
- Electronic publication date
- 08/05/2022
- Date published
- 05/16/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984320006802771
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