Methylation of cysteinyl leukotriene receptor 1 genes associates with lung function in asthmatics exposed to traffic-related air pollution

Autor: Nathan Rabinovitch, Meaghan J. Jones, Nicole Gladish, Anna V. Faino, Matthew Strand, Alexander M. Morin, Julie MacIsaac, David T. S. Lin, Paul R. Reynolds, Amrit Singh, Erwin W. Gelfand, Michael S. Kobor, Christopher Carlsten
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Epigenetics, Vol 16, Iss 2, Pp 177-185 (2021)
Druh dokumentu: article
ISSN: 1559-2294
1559-2308
15592294
DOI: 10.1080/15592294.2020.1790802
Popis: Air pollution is associated with early declines in lung function and increased levels of asthma-related cysteinyl leukotrienes (CysLT) but a biological pathway linking this rapid response has not been delineated. In this randomized controlled diesel exhaust (DE) challenge study of 16 adult asthmatics, increased exposure-attributable urinary leukotriene E4 (uLTE4, a biomarker of cysteinyl leukotriene production) was correlated (p = 0.04) with declines in forced expiratory volume in 1-second (FEV1) within 6 hours of exposure. Exposure-attributable uLTE4 increases were correlated (p = 0.02) with increased CysLT receptor 1 (CysLTR1) methylation in peripheral blood mononuclear cells which, in turn, was marginally correlated (p = 0.06) with decreased CysLTR1 expression. Decreased CysLTR1 expression was, in turn, correlated (p = 0.0007) with FEV1 declines. During the same time period, increased methylation of GPR17 (a negative regulator of CysLTR1) was observed after DE exposure (p = 0.02); this methylation increase was correlated (p = 0.001) with decreased CysLTR1 methylation which, in turn, was marginally correlated (p = 0.06) with increased CysLTR1 expression; increased CysLTR1 expression was correlated (p = 0.0007) with FEV1 increases. Collectively, these data delineate a potential mechanistic pathway linking increased DE exposure-attributable CysLT levels to lung function declines through changes in CysLTR1-related methylation and gene expression.
Databáze: Directory of Open Access Journals
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