Telomere length and genetic variant associations with interstitial lung disease progression and survival

Chad A. Newton, Justin M. Oldham, Brett Ley, Vikram Anand, Ayodeji Adegunsoye, Gabrielle Liu, Kiran Batra, Jose Torrealba, Julia Kozlitina, Craig Glazer, Mary E. Strek, Paul J. Wolters, Imre Noth, Christine K Garcia

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Abstract

Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF).In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator.The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of -0.05±0.29 and -0.04±0.25, respectively) is longer than that of IPF patients (-0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (-6.43% per year versus -0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (-0.14±0.27 versus -0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4-46.3 versus 14.1, 95% CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.

Original languageEnglish (US)
JournalThe European respiratory journal
Volume53
Issue number4
DOIs
StatePublished - Apr 1 2019

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Interstitial Lung Diseases
Telomere
Disease Progression
Leukocytes
Idiopathic Pulmonary Fibrosis
Survival
Gene Frequency
Transplants
Lung
Connective Tissue Diseases
Arthritis
Observational Studies
Rheumatoid Arthritis
Cohort Studies
Survival Rate

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Telomere length and genetic variant associations with interstitial lung disease progression and survival. / Newton, Chad A.; Oldham, Justin M.; Ley, Brett; Anand, Vikram; Adegunsoye, Ayodeji; Liu, Gabrielle; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig; Strek, Mary E.; Wolters, Paul J.; Noth, Imre; Garcia, Christine K.

In: The European respiratory journal, Vol. 53, No. 4, 01.04.2019.

Research output: Contribution to journalArticle

Newton, Chad A. ; Oldham, Justin M. ; Ley, Brett ; Anand, Vikram ; Adegunsoye, Ayodeji ; Liu, Gabrielle ; Batra, Kiran ; Torrealba, Jose ; Kozlitina, Julia ; Glazer, Craig ; Strek, Mary E. ; Wolters, Paul J. ; Noth, Imre ; Garcia, Christine K. / Telomere length and genetic variant associations with interstitial lung disease progression and survival. In: The European respiratory journal. 2019 ; Vol. 53, No. 4.
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abstract = "Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF).In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator.The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of -0.05±0.29 and -0.04±0.25, respectively) is longer than that of IPF patients (-0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (-6.43{\%} per year versus -0.86{\%} per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95{\%} CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95{\%} CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95{\%} CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (-0.14±0.27 versus -0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95{\%} CI 24.4-46.3 versus 14.1, 95{\%} CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.",
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AU - Liu, Gabrielle

AU - Batra, Kiran

AU - Torrealba, Jose

AU - Kozlitina, Julia

AU - Glazer, Craig

AU - Strek, Mary E.

AU - Wolters, Paul J.

AU - Noth, Imre

AU - Garcia, Christine K

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N2 - Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF).In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator.The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of -0.05±0.29 and -0.04±0.25, respectively) is longer than that of IPF patients (-0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (-6.43% per year versus -0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (-0.14±0.27 versus -0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4-46.3 versus 14.1, 95% CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.

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