Gene promoter methylation is associated with lung function in the elderly: The normative aging study

Lepeule, Johanna; Baccarelli, Andrea; Tarantini, Letizia; Motta, Valeria; Cantone, Laura; Litonjua, Augusto A.; Sparrow, David; Vokonas, Pantel; Schwartz, Joel

doi:10.4161/epi.7.3.19216

Cited by 50 publications

(59 citation statements)

References 56 publications

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“…Five studies [21–23, 25, 26] evaluated the association of lung function with DNA methylation and, of these, two (Qiu et al and Lange et al) also reported associations for COPD.…”

Section: Resultsmentioning

confidence: 99%

“…Pulmonary Clinics at these hospitals and associated hospitals served as additional source of participants [32]Post-bronchodilator FEV1/FVC < 0.7 and FEV1 < 70% predictedBell et al [22]2012UKTwins UKHealthy unselected volunteers who are a twin (MZ, DZ and singleton) representing the general populationParticipants recruited from media campaigns, initially only middle-aged women were included in the registry but from 1995 onwards, men and women >18 years of age were also recruited [28]Analysed lung function only (no COPD diagnosis) –FEV1 and FVCLepeule et al [25]2012USANormative AgeingHealthy male participants at enrolment, containing smokers and ex-smokers (Veterans Administration 1963 closed-cohort)Enrolled after an initial health screening determined that they were free of known chronic medical conditionsAnalysed lung function –FEV1, FVC, MMEF (did not specify pre-/post-bronchodilator)Lange et al [26]2012Boston (USA)Normative AgeingHealthy male participants at enrolment, containing smokers and ex-smokers (Veterans Administration 1963 closed-cohort)Enrolled after an initial health screening determined that they were free of known chronic medical conditionsGOLD stage II or higher (pre-bronchodilator FEV1/FVC < 0.7 and FEV1 < 80% predicted)Marioni et al [21]2015Scotland (UK)Lothian BirthChildhood inception cohort of ‘healthy b ’ participants with varying lung function, containing smokers, ex-smokers and never smokersIndividuals born in 1936 in the Lothian area were identified using the Community Health Index (registered at a general practitioner) or through media advertisements. The majority of the cohort were participants in the Scottish Mental Survey 1947 [27]Analysed lung function only (no COPD diagnosis)-FEV1Wielscher et al [24]2015AustriaN/ACOPD patients, GOLD 0 COPD patients and healthy controlsSelection of patient from Medical University of Vienna, 2008-2012Post-bronchodilator FEV1/FVC <0.7 Abbreviations : ICGN International COPD Genetics Network a Multi-centre: Cambridge, Copenhagen, Denver, Harvard, Holland, Italy, Liverpool, Nebraska, Spain, Vancouver EOCOPD: Early-onset COPD (Boston), AAT: Alpha-1-Antitrypsin, UK: United Kingdom, MZ: Monozygotic twin, DZ: Dizygotic twin, USA: United States of America, GOLD: Global Initiative for Chronic Obstructive Lung Disease b Healthy: participants free from chronic disease at enrolment, GOLD stage 0: FEV1/FVC ratio > 0.7 but with respiratory symptoms …”

Section: Resultsmentioning

confidence: 99%

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Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies

et al. 2017

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BackgroundEpigenetic variations in peripheral blood have potential as biomarkers for disease. This systematic review assesses the association of lung function and chronic obstructive pulmonary disease (COPD) with DNA methylation profiles in peripheral blood from population-based studies.MethodsOnline databases Medline, Embase, and Web of Science were searched. Google Scholar was searched to identify grey literature. After removing duplicate articles, 1155 articles were independently screened by two investigators. Peer reviewed reports on population-based studies that examined peripheral blood DNA methylation in participants with measured lung function (FEV1, FEV1/FVC ratio) or known COPD status were selected for full-text review. Six articles were suitable for inclusion. Information regarding study characteristics, designs, methodologies and conclusions was extracted. A narrative synthesis was performed based on published results.ResultsThree of the six articles assessed the association of COPD with DNA methylation, and two of these also included associations with lung function. Overall, five reports examined the association of lung function with DNA methylation profiles. Five of the six articles reported ‘significant’ results. However, no consistent CpG sites were identified across studies for COPD status or lung function values.ConclusionsDNA methylation patterns in peripheral blood from individuals with reduced lung function or COPD may be different to those in people with normal lung function. However, this systematic review did not find any consistent associations of lung function or COPD with differentially methylated CpG sites. Large studies with a longitudinal design to address reverse causality may prove a more fruitful area of research.Trial registrationPROSPERO 2016: CRD42016037352.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0397-3) contains supplementary material, which is available to authorized users.

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“…Five studies [21–23, 25, 26] evaluated the association of lung function with DNA methylation and, of these, two (Qiu et al and Lange et al) also reported associations for COPD.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies

et al. 2017

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“…In the Normative Aging Study, we generated pyrosequencing-based methylation data for nine genes across pathways related to oxidation, blood clotting, and inflammation (Bind et al 2012; Lepeule et al 2012, 2014). We chose to focus our analysis on the four inflammatory genes included in these genes, including two inflammatory cytokines ( IFN- γ and IL-6 ), intercellular adhesion molecule 1 ( ICAM-1 ), and Toll-like receptor 2 ( TLR-2 ).…”

Section: Methodsmentioning

confidence: 99%

Particulate Air Pollution and Fasting Blood Glucose in Nondiabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000–2011

Peng

Bind

Colicino

et al. 2016

Environ Health Perspect

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115

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Background:Among nondiabetic individuals, higher fasting blood glucose (FBG) independently predicts diabetes risk, cardiovascular disease, and dementia. Ambient PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) is an emerging determinant of glucose dysregulation. PM2.5 effects and mechanisms are understudied among nondiabetic individuals.Objectives:Our goals were to investigate whether PM2.5 is associated with an increase in FBG and to explore potential mediating roles of epigenetic gene regulation.Methods:In 551 nondiabetic participants in the Normative Aging Study, we measured FBG, and DNA methylation of four inflammatory genes (IFN-γ, IL-6, ICAM-1, and TLR-2), up to four times between 2000 and 2011 (median = 2). We estimated short- and medium-term (1-, 7-, and 28-day preceding each clinical visit) ambient PM2.5 at each participant’s address using a validated hybrid land-use regression satellite-based model. We fitted covariate-adjusted regression models accounting for repeated measures.Results:Mean FBG was 99.8 mg/dL (SD = 10.7), 18% of the participants had impaired fasting glucose (IFG; i.e., 100–125 mg/dL FBG) at first visit. Interquartile increases in 1-, 7-, and 28-day PM2.5 were associated with 0.57 mg/dL (95% CI: 0.02, 1.11, p = 0.04), 1.02 mg/dL (95% CI: 0.41, 1.63, p = 0.001), and 0.89 mg/dL (95% CI: 0.32, 1.47, p = 0.003) higher FBG, respectively. The same PM2.5 metrics were associated with 13% (95% CI: –3%, 33%, p = 0.12), 27% (95% CI: 6%, 52%, p = 0.01) and 32% (95% CI: 10%, 58%, p = 0.003) higher odds of IFG, respectively. PM2.5 was negatively correlated with ICAM-1 methylation (p = 0.01), but not with other genes. Mediation analysis estimated that ICAM-1 methylation mediated 9% of the association of 28-day PM2.5 with FBG.Conclusions:Among nondiabetics, short- and medium-term PM2.5 were associated with higher FBG. Mediation analysis indicated that part of this association was mediated by ICAM-1 promoter methylation.Citation:Peng C, Bind MA, Colicino E, Kloog I, Byun HM, Cantone L, Trevisi L, Zhong J, Brennan K, Dereix AE, Vokonas PS, Coull BA, Schwartz JD, Baccarelli AA. 2016. Particulate air pollution and fasting blood glucose in nondiabetic individuals: associations and epigenetic mediation in the Normative Aging Study, 2000–2011. Environ Health Perspect 124:1715–1721; http://dx.doi.org/10.1289/EHP183

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“…Studies in humans have reported associations between blood DNA methylation and cardiovascular diseases (Stenvinkel et al 2007), respiratory health (Lepeule et al 2012), and survival (Baccarelli et al 2010). …”

Section: Introductionmentioning

confidence: 99%

Epigenetic Influences on Associations between Air Pollutants and Lung Function in Elderly Men: The Normative Aging Study

Lepeule¹,

Bind²,

Baccarelli³

et al. 2014

Environ Health Perspect

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106

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Background: Few studies have been performed on pulmonary effects of air pollution in the elderly—a vulnerable population with low reserve capacity—and mechanisms and susceptibility factors for potential effects are unclear.Objectives: We evaluated the lag structure of air pollutant associations with lung function and potential effect modification by DNA methylation (< or ≥ median) at 26 individual CpG sites in nine candidate genes in a well-characterized cohort of elderly men.Methods: We measured forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and blood DNA methylation one to four times between 1999 and 2009 in 776 men from the Normative Aging Study. Air pollution was measured at fixed monitors 4 hr to 28 days before lung function tests. We used linear mixed-effects models to estimate the main effects of air pollutants and effect modification by DNA methylation.Results: An interquartile range (IQR) increase in subchronic exposure (3 to 28 days cumulated), but not in acute exposure (during the previous 4 hr, or the current or previous day), to black carbon, total and nontraffic particles with aerodynamic diameter ≤ 2.5 μm (PM2.5), carbon monoxide, and nitrogen dioxide was associated with a 1–5% decrease in FVC and FEV1 (p < 0.05). Slope estimates were greater for FVC than FEV1, and increased with cumulative exposure. The estimates slopes for air pollutants (28 days cumulated) were higher in participants with low (< median) methylation in TLR2 at position 2 and position 5 and high (≥ median) methylation in GCR.Conclusions: Subchronic exposure to traffic-related pollutants was associated with significantly reduced lung function in the elderly; nontraffic pollutants (particles, ozone) had weaker associations. Epigenetic mechanisms related to inflammation and immunity may influence these associations.Citation: Lepeule J, Bind MAC, Baccarelli AA, Koutrakis P, Tarantini L, Litonjua A, Sparrow D, Vokonas P, Schwartz JD. 2014. Epigenetic influences on associations between air pollutants and lung function in elderly men: the Normative Aging Study. Environ Health Perspect 122:566–572; http://dx.doi.org/10.1289/ehp.1206458

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Gene promoter methylation is associated with lung function in the elderly: The normative aging study

Abstract: (2012) Gene promoter methylation is associated with lung function in the elderly: The normative aging study, Epigenetics, 7:3, 261-269,

Cited by 50 publications

References 56 publications

Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies

Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies

Particulate Air Pollution and Fasting Blood Glucose in Nondiabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000–2011

Epigenetic Influences on Associations between Air Pollutants and Lung Function in Elderly Men: The Normative Aging Study

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