MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study

Autor:	John S Kim, Ani W Manichaikul, Eric A Hoffman, Pallavi Balte, Michaela R Anderson, Elana J Bernstein, Purnema Madahar, Elizabeth C Oelsner, Steven M Kawut, Artur Wysoczanski, Andrew F Laine, Ayodeji Adegunsoye, Jennie Z Ma, Margaret A Taub, Rasika A Mathias, Stephen S Rich, Jerome I Rotter, Imre Noth, Christine Kim Garcia, R Graham Barr, Anna J Podolanczuk
Rok vydání:	2023
Předmět:	Pulmonary and Respiratory Medicine Lung Diseases Adult Genotype Clinical Sciences Respiratory System Telomere Mucin-5B Imaging/CT MRI etc Article Interstitial Fibrosis Good Health and Well Being Clinical Research Genetics Humans Interstitial Lung
Zdroj:	Thorax, vol 78, iss 6 Thorax
Popis:	BackgroundTheMUC5Bpromoter 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.MethodsWe used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1–6 (2000–2018)) andMUC5Bgenotype (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 ofMUC5Brisk 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).ResultsTheMUC5Brisk 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.ConclusionsLongitudinal increases in HAAs were associated with theMUC5Brisk allele and a higher risk of death and ILD.
Databáze:	OpenAIRE
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