F2RL3 methylation as a biomarker of current and lifetime smoking exposures

Background: Recent genome-wide DNA methylation studies have found a pronounced difference in methylation of the F2RL3 gene (also known as PAR-4) in blood DNA according to smoking exposure. Knowledge on the variation of F2RL3 methylation by various degrees of smoking exposure is still very sparse.Obj...

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Hauptverfasser: Zhang, Yan (VerfasserIn) , Yang, Rongxi (VerfasserIn) , Burwinkel, Barbara (VerfasserIn) , Breitling, Lutz Philipp (VerfasserIn) , Brenner, Hermann (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1 February 2014
In: Environmental health perspectives
Year: 2014, Jahrgang: 122, Heft: 2, Pages: 131-137
ISSN:1552-9924
DOI:10.1289/ehp.1306937
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1289/ehp.1306937
Verlag, lizenzpflichtig, Volltext: https://ehp.niehs.nih.gov/doi/10.1289/ehp.1306937
Volltext
Verfasserangaben:Yan Zhang, Rongxi Yang, Barbara Burwinkel, Lutz P. Breitling, and Hermann Brenner

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520 |a Background: Recent genome-wide DNA methylation studies have found a pronounced difference in methylation of the F2RL3 gene (also known as PAR-4) in blood DNA according to smoking exposure. Knowledge on the variation of F2RL3 methylation by various degrees of smoking exposure is still very sparse.Objectives: We aimed to assess dose-response relationships of current and lifetime active smoking exposure with F2RL3 methylation.Methods: In a large population-based study, we quantified blood DNA methylation at F2RL3 for 3,588 participants using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations of smoking exposure with methylation intensity were examined by multiple linear regression, controlling for potential confounding factors and paying particular attention to dose-response patterns with respect to current and lifetime smoking exposure as well as time since cessation of smoking.Results: F2RL3 methylation intensity showed a strong association with smoking status (p < 0.0001), which persisted after controlling for potential confounding factors. Clear inverse dose-response relationships with F2RL3 methylation intensity were seen for both current intensity and lifetime pack-years of smoking. Among former smokers, F2RL3 methylation intensity increased gradually from levels close to those of current smokers for recent quitters to levels close to never smokers for long-term (> 20 years) quitters.Conclusions: F2RL3 methylation is a promising biomarker for both current and long-term past tobacco exposure, and its predictive value for smoking-related diseases warrants further exploration.Citation: Zhang Y, Yang R, Burwinkel B, Breitling LP, Brenner H. 2014. F2RL3 methylation as a biomarker of current and lifetime smoking exposures. Environ Health Perspect 122:131-137;  http://dx.doi.org/10.1289/ehp.1306937 
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