Berita Kesehatan
Telomere Length and Genetic Variant Associations with Interstitial Lung Disease Progression and Surv
Jumat, 29 Mar 2019 08:28:24
Chad A. NewtonJustin M. OldhamBrett LeyVikram AnandAyodeji AdegunsoyeGabrielle LiuKiran BatraJose TorrealbaJulia KozlitinaCraig GlazerMary E. StrekPaul J. WoltersImre NothChristine Kim Garcia
European Respiratory Journal 2019; DOI: 10.1183/13993003.01641-2018

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.

LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of −0.05, [sd 0.29] and −0.04 [0.25], respectively) are longer than IPF (−0.17 [0.32]). For IPAF, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (−6.43%/year versus−0.86%/year, p<0.0001) and worse transplant-free survival (HR 2.97 [95% CI 1.70–5.20], p=0.00014). The MUC5B rs35705950 minor allele frequency is greater for IPAF (23.2 [95% CI 18.8–28.2], p<0.0001) than controls and is associated with worse transplant-free IPAF survival (HR 1.92, [95% CI 1.18–3.13], p=0.0091). Rheumatoid arthritis-associated ILD (RA-ILD) has shorter LTL than non-RA CTD-ILD (−0.14 [sd 0.27] versus −0.01 [0.23], p=0.00055) and higher MUC5B minor allele frequency (34.6 [95% CI 24.4–46.3] versus 14.1 [9.8–20.0], p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.

LTL and MUC5B minor allele frequency have different associations with lung function progression and survival for IPAF and CTD-ILD.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Newton reports no relevant conflicts of interest.

Conflict of interest: Dr. Oldham reports grants from NHLBI, personal fees from Genentech, personal fees from BI, outside the submitted work.

Conflict of interest: Dr. Ley has nothing to disclose.

Conflict of interest: Dr. Anand has nothing to disclose.

Conflict of interest: Dr. Adegunsoye reports having received speaking fees and honoraria for advisory boards with Boehringer Ingelheim related to IPF within the last 12 months.

Conflict of interest: Dr. Liu has nothing to disclose.

Conflict of interest: Dr. Batra has nothing to disclose.

Conflict of interest: Dr. Torrealba reports personal fees from Roche – Ventana, personal fees from AbbVie, outside the submitted work.

Conflict of interest: Dr. Kozlitina has nothing to disclose.

Conflict of interest: Dr. Glaser reports and I am on the speaker's bureau for genentech there is no discussion of therapy in this paper but in the interest of full discloser I wanted to include.

Conflict of interest: Dr. Strek reports grants from Boehringer-Ingelheim, grants from Genentech-Roche, grants from Gilead, grants from MedImmune, personal fees from Boehringer-Ingelheim, outside the submitted work.

Conflict of interest: Dr. Wolters reports grants from medimmune, grants from Genentech, personal fees from Roche, personal fees from Boehringer Ingelheim, outside the submitted work.

Conflict of interest: Dr. North reports personal fees from Boehringer Ingelheim, personal fees from Genentech, personal fees from Sanofi Aventis, personal fees from Global Blood Therapeutics, outside the submitted work; In addition, Dr. Noth has a patent TOLLIP and IPF pharmacogenomics pending.

Conflict of interest: Dr. Garcia has no relevant conflicts of interest.