ABSTRACT: Short-term elevations in ambient fine particulate matter (PM(2.5)) may increase resting systolic (SBP) and diastolic (DBP) blood pressures, but whether PM(2.5) alters hemodynamic responses to orthostatic challenge has not been studied in detail. We repeatedly measured SBP and DBP during supine rest and 1 and 3 minutes after standing among 747 elderly (aged 78.3±5.3 years, mean±SD) participants from a prospective cohort study. We used linear mixed models to assess the association between change in SBP (ΔSBP=standing SBP-supine SBP) and DBP (ΔDBP) on standing and mean PM(2.5) levels over the preceding 1 to 28 days, adjusting for meteorologic covariates, temporal trends, and medical history. We observed a 1.4-mm Hg (95% CI: 0.0-2.8 mm Hg; P=0.046) higher ΔSBP and a 0.7-mm Hg (95% CI: 0.0-1.4 mm Hg; P=0.053) higher ΔDBP at 1 minute of standing per interquartile range increase (3.8 μg/m(3)) in mean PM(2.5) levels in the past 7 days. ΔSBP and ΔDBP measured 3 minutes after standing were not associated with PM(2.5). Resting DBP (but not SBP or pulse pressure) was positively associated with PM(2.5) at longer averaging periods. Responses were more strongly associated with black carbon than sulfate levels. These associations did not differ significantly according to hypertension status, obesity, diabetes mellitus, or sex. These results suggest that ambient particles can increase resting DBP and exaggerate blood pressure responses to postural changes in elderly people. Increased vasoreactivity during posture change may be responsible, in part, for the adverse effect of ambient particles on cardiovascular health.
Hypertension 03/2012; 59(3):558-63. · 6.21 Impact Factor
ABSTRACT: Fetal programming describes the theory linking environmental conditions during embryonic and fetal development with risk of diseases later in life. Environmental insults in utero may lead to changes in epigenetic mechanisms potentially affecting fetal development.
We examined associations between in utero exposures, infant growth, and methylation of repetitive elements and gene-associated DNA in human term placenta tissue samples.
Placental tissues and associated demographic and clinical data were obtained from subjects delivering at Women and Infants Hospital in Providence, Rhode Island (USA). Methylation levels of long interspersed nuclear element-1 (LINE-1) and the Alu element AluYb8 were determined in 380 placental samples from term deliveries using bisulfite pyrosequencing. Genomewide DNA methylation profiles were obtained in a subset of 184 samples using the Illumina Infinium HumanMethylation27 BeadArray. Multiple linear regression, model-based clustering methods, and gene set enrichment analysis examined the association between birth weight percentile, demographic variables, and repetitive element methylation and gene-associated CpG locus methylation.
LINE-1 and AluYb8 methylation levels were found to be significantly positively associated with birth weight percentile (p = 0.01 and p < 0.0001, respectively) and were found to differ significantly among infants exposed to tobacco smoke and alcohol. Increased placental AluYb8 methylation was positively associated with average methylation among CpG loci found in polycomb group target genes; developmentally related transcription factor binding sites were overrepresented for differentially methylated loci associated with both elements.
Our results suggest that repetitive element methylation markers, most notably AluYb8 methylation, may be susceptible to epigenetic alterations resulting from the intrauterine environment and play a critical role in mediating placenta function, and may ultimately inform on the developmental basis of health and disease.
Environmental Health Perspectives 02/2012; 120(2):296-302. · 7.04 Impact Factor
ABSTRACT: The association between secondhand smoke (SHS) exposure and bladder cancer is inconclusive. Epigenetic alterations in bladder tumors have been linked to primary cigarette smoking and could add to the biological plausibility of an association between SHS exposure and bladder cancer.
SHS exposure is associated with DNA methylation in bladder tumors.
Using an array-based approach, we profiled DNA methylation from never smoking cases of incident bladder cancer. Analyses examined associations between individual loci's methylation with SHS variables (exposure in adulthood, childhood, occupationally, and total exposure). A canonical pathway analysis was used to find pathways significantly associated with each SHS exposure type.
There is a trend toward increased methylation of numerous CpG loci with increasing exposure to adulthood, occupational, and total SHS. Discrete associations between methylation extent of several CpG loci and SHS exposures demonstrated significantly increased methylation of these loci across all types of SHS exposure. CpGs with SHS-related methylation alterations were associated with genes in pathways involved in carcinogenesis, immune modulation, and immune signaling.
Exposures to SHS in adulthood, childhood, occupationally, and in total are each significantly associated with changes in DNA methylation of several CpG loci in bladder tumors, adding biological plausibility to SHS as a risk factor for bladder cancer.
Cancer Causes and Control 06/2011; 22(8):1205-13. · 2.88 Impact Factor