The effects of fine particulate matter constituents on exhaled nitric oxide and DNA methylation in the arginase–nitric oxide synthase pathway

Zhang, Qingli; Wang, Weidong; Niu, Yue; Xia, Yongde; Lei, Xiaoning; Huo, Juntao; Zhao, Qianbiao; Zhang, Yihua; Duan, Yusen; Cai, Jing; Zhao, Ying; Li, Weihua; Chen, Renjie; Fu, Qingyan; Kan, Haidong

doi:10.1016/j.envint.2019.105019

Cited by 36 publications

(43 citation statements)

References 30 publications

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“…Unlike previous studies, we did not nd signi cant changes in the methylation level in other NOS and ARG isoforms in response to TRAP (10). These inconsistent results could be due to several differences between our study and the previous studies, including differences in the study populations (children vs. adults, and asthma vs. other health conditions), exposure assessment approaches (personal vs. xed-site monitoring) and the selection of CpG sites tested (8,10,11,21,22).…”

Section: Discussioncontrasting

confidence: 99%

“…Using the same cohort, Breton et al found signi cantly lower NOS2A methylation and higher NOS3 methylation in response to acute and chronic exposure to particulate matter (10). Similar results were observed in panel studies of exposure to PM in China among 43 healthy adults and 30 adults with chronic obstructive pulmonary disease (8,11). However, one panel study revealed that occupational exposure to ne PM was positively associated with increased NOS2A methylation in 38 male boilermaker welders (22).…”

Section: Discussionmentioning

confidence: 59%

“…Studies have found similar gene expression, as well as methylation level in buccal cells and cells from the respiratory tract in response to tobacco, supporting the potential of the oral epithelium as a surrogate tissue for respiratory epithelium (25,26). Other studies, noted above, have found associations between exposure to air pollution and changes in methylation in NOS genes from buccal cells (9)(10)(11)(12)21).…”

Section: Discussionmentioning

confidence: 64%

“…First, the temporal sequence of TRAP, NOS and ARG methylation and FeNO is necessary when inferring causality. However, only ve observational studies have examined the temporality (8)(9)(10)(11)(12). Second, all but one of these studies relied on xed-site measurements in assessing individual-level exposure, which may have biased associations between TRAP and respiratory outcomes compared to personal exposure measurements (12).…”

Section: Introductionmentioning

confidence: 99%

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Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide and DNA Methylation in Arginase and Nitric Oxide Synthase in Children with Asthma

Fang

Baptista

et al. 2020

Preprint

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Background Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma. Methods We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level. Results Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0–6 hours while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13–24 hours and lag 0–24 hours, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed. Conclusions Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

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Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide and DNA Methylation in Arginase and Nitric Oxide Synthase in Children with Asthma

Fang

Baptista

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Using the same cohort, Breton et al found signi cantly lower NOS2A methylation and higher NOS3 methylation in response to acute and chronic exposure to particulate matter (10). Similar results were observed in panel studies of exposure to PM in China among 43 healthy adults and 30 adults with chronic obstructive pulmonary disease (8,11) . However, one panel study revealed that occupational exposure to ne PM was positively associated with increased NOS2A methylation in 38 male boilermaker welders (23).…”

Section: Discussionsupporting

confidence: 57%

Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide and DNA Methylation in Arginase and Nitric Oxide Synthase in Children with Asthma

Fang

Baptista

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma.Methods: We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level.Results: Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0–6 hours while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13-24 hours and lag 0-24 hours, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed.Conclusions: Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.

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Asthma Epigenetics: Elucidating an Expanding Paradigm

Miller

Chen

2022

Epigenetic Epidemiology

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The effects of fine particulate matter constituents on exhaled nitric oxide and DNA methylation in the arginase–nitric oxide synthase pathway

Cited by 36 publications

References 30 publications

Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide and DNA Methylation in Arginase and Nitric Oxide Synthase in Children with Asthma

Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide and DNA Methylation in Arginase and Nitric Oxide Synthase in Children with Asthma

Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide and DNA Methylation in Arginase and Nitric Oxide Synthase in Children with Asthma

Asthma Epigenetics: Elucidating an Expanding Paradigm

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