Lung Function and Gene Expression of Pathogen Recognition Pathway Receptors: the Cardia Lung Study

Ramya Ramasubramanian, Ravi Kalhan, David R. Jacobs, George R. Washko, Lifang Hou, Myron D. Gross, Weihua Guan, Bharat Thyagarajan

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC) and FEV1/FVC). We studied gene expression levels and lung function in the Coronary Artery Risk Development in Young Adults study. Spirometry testing was used to measure lung function and gene expression levels were measured using the Nanostring platform. Multivariate linear regression models were used to study the association between lung function measured at year 30, 10-year decline from year 20 to year 30, and gene expression levels (highest quartile divided into two levels – 75th to 95th and>95th to 100th percentile) adjusting for center, smoking and BMI, measured at year 25. Year 30 FEV1 and FVC were lower in the highest level of TLR5 compared to the lowest quartile with difference of 4.00% (p for trend: 0.04) and 3.90% (p for trend: 0.05), respectively. The 10-year decline of FEV1 was faster in the highest level of CCR1 as compared to the lowest quartile with a difference of 1.69% (p for trend: 0.01). There was no association between gene expression and FEV1/FVC. Higher gene expression levels in TLR5 and CCR1 are associated with lower lung function and faster decline in FEV1 over 10 years, in a threshold manner, providing new insights into the role of inflammation in lung function.

Original languageEnglish (US)
Article number9360
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
The CARDIA study is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI); the Intramural Research Program of the National Institute on Aging (NIA); and an intra‐agency agreement between the NIA and NHLBI (AG0005) and grant R01 HL122477 (to Kalhan). This manuscript has been reviewed by CARDIA for scientific content.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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