Allergen sensitization is associated with increased dna methylation in older men

Background: Variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression and may ultimately contribute to complex diseases such as asthma and allergies. We examined the association of asthma and allergic phenotypes with DNA methylation levels of retrotransposon-derived elements. Methods: We used data from 704 men (mean age 73 years) in the longitudinal Normative Aging Study to assess the relationship between asthma, allergic phenotypes and DNA methylation levels of the retrotransposon-derived elements Alu and long interspersed nuclear element (LINE)-1. Retrotransposons represent a large fraction of the genome (>30%) and are heavily methylated to prevent expression. Percent methylation of Alu and LINE-1 elements in peripheral white blood cells was quantified using PCR pyrosequencing. Data on sensitization to common allergens from skin prick testing, asthma and methacholine responsiveness were gathered approximately 8 years prior to DNA methylation analysis. Results: Prior allergen sensitization was associated with increased methylation of Alu (\u3b2 = 0.32 for sensitized vs. nonsensitized patients; p = 0.003) in models adjusted for pack-years of smoking, body mass index, current smoking, air pollutants, percentage of eosinophils, white blood cell count and age. Of the men interviewed, 5% of subjects reported a diagnosis of asthma. Neither Alu nor LINE-1 methylation was associated with asthma. Conclusions: These data suggest that increased DNA methylation of repetitive elements may be associated with allergen sensitization but does not appear to be associated with asthma. Future work is needed to identify potential underlying mechanisms for these relationships

Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals : the Normative Aging Study

BACKGROUND: Global genomic hypomethylation is a common epigenetic event in cancer that mostly results from hypomethylation of repetitive DNA elements. Case-control studies have associated blood leukocyte DNA hypomethylation with several cancers. Because samples in case-control studies are collected after disease development, whether DNA hypomethylation is causal or just associated with cancer development is still unclear. METHODS: In 722 elderly subjects from the Normative Aging Study cohort, we examined whether DNA methylation in repetitive elements (Alu, LINE-1) was associated with cancer incidence (30 new cases, median follow-up: 89 months), prevalence (205 baseline cases), and mortality (28 deaths, median follow-up: 85 months). DNA methylation was measured by bisulfite pyrosequencing. RESULTS: Individuals with low LINE-1 methylation (<median) had a 3.0-fold (95%CI 1.3-6.9) increased incidence of all cancers combined. LINE-1 and Alu methylation were not significantly associated with cancer prevalence at baseline (all cancers combined). However, individuals with low LINE-1 methylation (<median) had a 3.2-fold (95% CI 1.4-7.5) higher prevalence of lung cancer. Individuals with low LINE-1 or Alu methylation (<median) had increased cancer mortality (HR = 3.2, 95%CI 1.3-7.9 for LINE-1; HR = 2.5, 95%CI 1.1-5.8 for Alu). CONCLUSION: These findings suggest that individuals with lower repetitive element methylation are at high risk of developing and dying from cancer

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

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.120645

Air Pollution and ST-Segment Depression in Elderly Subjects

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post-exercise rest, an elevated BC level was associated with −0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic

Plasma metabolite profiles in children with current asthma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146270/1/cea13183.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146270/2/cea13183_am.pd

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Association between 24-Hour Urinary Cadmium and Pulmonary Function among Community-Exposed Men: The VA Normative Aging Study

Background: High levels of cadmium exposure are known to cause emphysema in occupationally exposed workers, but little has been reported to date on the association between chronic environmental cadmium exposure and pulmonary function. Objective: In this study we examined the association between pulmonary function and cadmium body burden in a subcohort of the Normative Aging Study, a community-based study of aging. Methods: We examined 96 men who had cadmium measured in single 24-hr urinary specimens collected in 1994–1995 and who had one to three tests of pulmonary function between 1994 and 2002 (a total of 222 observations). We used mixed-effect models to predict pulmonary function based on individual 24-hr urinary cadmium output, adjusted for age, height, time elapsed from the baseline, and smoking status. We assessed effect modification by smoking status. Results: Among all subjects, a single log-unit increase in baseline urinary cadmium was inversely associated with forced expiratory volume in 1 sec (FEV1) percent predicted [β = −7.56%; 95% confidence interval (CI) −13.59% to −1.53%]; forced vital capacity (FVC) percent predicted (β = −2.70%; 95% CI −7.39% to 1.99%), and FEV1/FVC ratio (β = −4.13%; 95% CI −7.61% to −0.66%). In models including an interaction between urinary cadmium and smoking status, there was a graded, statistically significant reduction in FEV1/FVC ratio across smoking status in association with urinary cadmium. Conclusions: This study suggests that chronic cadmium exposure is associated with reduced pulmonary function, and cigarette smoking modifies this association. These results should be interpreted with caution because the sample size is small, and further studies are needed to confirm our findings

Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10-8) and PPP4R4/SERPINA1 (P = 1.0131028) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, ~0.6), and accounted for a mean 0.9–1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function

Peak expiratory flow rate shows a gender-specific association with vitamin D deficiency

Context: To our knowledge, no previous studies examined the longitudinal relationship between vitamin D status and pulmonary function in a population-based sample of older persons. Objective: Our objective was to examine the cross-sectional as well as the longitudinal relationship between vitamin D status and peak expiratory flow rate (PEFR) in a representative sample of the Dutch older population. Design, Setting, and Participants: Participants included men and women in the Longitudinal Aging Study Amsterdam, an ongoing cohort study in older people. Main Outcome Measure: PEFR was measured using the mini-Wright peak flow meter. Results: Men with serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (25 nmol/liter) had a significantly lower PEFR in the cross-sectional analyses, and men with serum 25-OHD levels below 20 ng/ml (50 nmol/liter) had a significantly lower PEFR in the longitudinal analyses as compared with men with serum 25-OHD levels above 30 ng/ml (75 nmol/liter) (cross-sectional: β = -47.0, P = 0.01 for serum 25-OHD<10 ng/ml; longitudinal: β = -45.0, P<0.01 for serum 25-OHD<10 ng/ml; and β = -20.2, P = 0.03 for serum 25-OHD = 10-20 ng/ml in the fully adjusted models). Physical performance (β = -32.5, P = 0.08 for serum 25-OHD<10 ng/ml) and grip strength (β = -40.0, P = 0.03 for serum 25-OHD <10 ng/ml) partly mediated the cross-sectional associations but not the longitudinal associations. In women, statistically significant associations between 25-OHD and PEFR were observed in the cross-sectional analyses after adjustment for age and season of blood collection but not in the fully adjusted models or in the longitudinal analyses. Conclusions: A strong relationship between serum 25-OHD and PEFR was observed in older men, both in the cross-sectional as well as longitudinal analyses, but not in older women. The association in men could partly be explained by physical performance and muscle strength. Copyright © 2012 by The Endocrine Society