Evidence map›Paper›PMID 22055874›Full record

ArticleThe Journal of allergy and clinical immunology2012

Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels in children.

Muhammad T Salam, Hyang-Min Byun, Fred Lurmann, Carrie V Breton, Xinhui Wang, Sandrah P Eckel, Frank D Gilliland

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02469428 (Epigenetic Effect Modifications With Ozone Exposure on Healthy Volunteers), which is not on this map. Cited by 67 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 3 pooled it
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02469428 nacompletednot on this mapstarted 2013, after this paper: background citation

Epigenetic Effect Modifications With Ozone Exposure on Healthy Volunteers

TypeinterventionalSponsorEnvironmental Protection Agency (EPA)Ran2013 to 2018Enrolled14ConditionsExposure to Environmental Pollution, Non-occupationalArmsClean air, Ozone
3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 131 citations in OpenAlex.

  1. Pooled it
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  8. Long-term PMPediatric research · 2025
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Muhammad T SalamDepartment of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, Calif 90089, USA. msalam@usc.edu
Hyang-Min Byun
Fred Lurmann
Carrie V Breton
Xinhui Wang
Sandrah P Eckel
Frank D Gilliland
University of Southern California · USHarvard University · USSonoma Technology (United States) · US

Funding

Translational Research Support CoreP30ES007048 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Joseph Leo Wiemels · 1996 to 2026
$46.4M
Urban Air Pollution and Children's Respiratory HealthP01ES011627 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AVOL, EDWARD · 2002 to 2011
$30.2M
Urban Air Pollution &Persistent Early Life AsthmaP01ES009581 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GILLILAND, FRANK D. · 1999 to 2010
$6.8M
FACTORS IN CHILDHOOD LUNG SUSCEPTIBILITY TO POLLUTIONR01HL061768 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GILLILAND, FRANK D. · 1999 to 2008
$4.4M
Air Pollution, Inflammation and New Onset AsthmaR01HL076647 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GILLILAND, FRANK D. · 2005 to 2009
$3.6M
NHLBI NIH HHS 5R01HL61768NHLBI NIH HHS 5R01HL76647NHLBI NIH HHS R01 HL061768NHLBI NIH HHS R01 HL076647NIEHS NIH HHS 5P01ES009581NIEHS NIH HHS 5P01ES011627NIEHS NIH HHS 5P30ES007048NIEHS NIH HHS P01 ES009581NIEHS NIH HHS P01 ES011627NIEHS NIH HHS P30 ES007048ORD VA RD831861-01PHS HHS R826708-01
6 · The paper itself

Abstract

backgroundInducible nitric oxide synthase (iNOS; encoded by nitric oxide synthase isoform 2 [NOS2]) is the major enzyme for nitric oxide synthesis in airways. As such, measurement of fractional concentration of exhaled nitric oxide (Feno) provides an in vivo assessment of iNOS activity. Short-term exposure to air pollution, haplotypes, and DNA methylation in the NOS2 promoter has been associated independently with iNOS expression, Feno levels, or both.

objectiveWe aimed to examine the effects of ambient air pollutants, NOS2 promoter haplotypes, and NOS2 promoter methylation on Feno levels in children.

methodsWe selected 940 participants in the Children's Health Study who provided buccal samples and had undergone Feno measurement on the same day. DNA methylation was measured with a bisulfite-PCR Pyrosequencing assay. Seven single nucleotide polymorphisms captured the haplotype diversity in the NOS2 promoter. Average particulate matter with an aerodynamic diameter of 2.5 μm or less (PM(2.5)) and 10 μm (PM(10)) or less and ozone and nitrogen dioxide levels 7 days before Feno measurement were estimated based on air pollution data obtained at central monitoring sites.

resultsWe found interrelated effects of PM(2.5), NOS2 promoter haplotypes, and iNOS methylation on Feno levels. Increased 7-day average PM(2.5) exposure was associated with lower iNOS methylation (P = .01). NOS2 promoter haplotypes were globally associated with NOS2 promoter methylation (P = 6.2 × 10(-8)). There was interaction among 1 common promoter haplotype, iNOS methylation level, and PM(2.5) exposure on Feno levels (P(interaction) = .00007).

conclusionPromoter variants in NOS2 and short-term PM(2.5) exposure affect iNOS methylation. This is one of the first studies showing contributions of genetic and epigenetic variations in air pollution-mediated phenotype expression.

Indexed as

Epigenesis, GeneticPromoter Regions, GeneticAdolescentAdultAir PollutantsAir PollutionChildDNA MethylationEnvironmental ExposureExhalationFemaleGene-Environment InteractionHaplotypesHumansMaleNitric OxideAir PollutantsNitric OxideNitric Oxide Synthase Type IIParticulate Matter

Identifiers

PMID22055874
PMCPMC3487398
OpenAlexW2153129506

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.