TY - JOUR
T1 - Differential DNA methylation and PM2.5 species in a 450K epigenome-wide association study
AU - Dai, Lingzhen
AU - Mehta, Amar
AU - Mordukhovich, Irina
AU - Just, Allan C.
AU - Shen, Jincheng
AU - Hou, Lifang
AU - Koutrakis, Petros
AU - Sparrow, David
AU - Vokonas, Pantel S.
AU - Baccarelli, Andrea A.
AU - Schwartz, Joel D.
N1 - Funding Information:
This work was supported by the National Institute of Environmental Health Sciences ES000002, ES021733 and ES015172–01 and the US. Environmental Protection Agency RD-83587201. A.J. was supported by the National Institute of Environmental Health Sciences K99 ES023450. D.S. was supported by a VA Research Career Scientist Award. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Centers of the US. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts.
Publisher Copyright:
© 2017 Taylor & Francis Group, LLC.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects. Bonferroni correction was applied to adjust for multiple comparisons. Bioinformatics analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was also performed. We observed 20 Bonferroni significant (P-value < 9.4× 10−9) CpGs for Fe, 8 for Ni, and 1 for V. Particularly, methylation at Schlafen Family Member 11 (SLFN11) cg10911913 was positively associated with measured levels of all 3 species. The SLFN11 gene codes for an interferon-induced protein that inhibits retroviruses and sensitizes cancer cells to DNA-damaging agents. Bioinformatics analysis suggests that gene targets may be relevant to pathways including cancers, signal transduction, and cell growth and death. Ours is the first study to examine the epigenome-wide association between ambient particles species and DNA methylation. We found that long-term exposures to specific components of ambient particle pollution, especially particles emitted during oil combustion, were associated with methylation changes in genes relevant to immune responses. Our findings provide insight into potential biologic mechanisms on an epigenetic level.
AB - Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects. Bonferroni correction was applied to adjust for multiple comparisons. Bioinformatics analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was also performed. We observed 20 Bonferroni significant (P-value < 9.4× 10−9) CpGs for Fe, 8 for Ni, and 1 for V. Particularly, methylation at Schlafen Family Member 11 (SLFN11) cg10911913 was positively associated with measured levels of all 3 species. The SLFN11 gene codes for an interferon-induced protein that inhibits retroviruses and sensitizes cancer cells to DNA-damaging agents. Bioinformatics analysis suggests that gene targets may be relevant to pathways including cancers, signal transduction, and cell growth and death. Ours is the first study to examine the epigenome-wide association between ambient particles species and DNA methylation. We found that long-term exposures to specific components of ambient particle pollution, especially particles emitted during oil combustion, were associated with methylation changes in genes relevant to immune responses. Our findings provide insight into potential biologic mechanisms on an epigenetic level.
KW - Ambient particulate matter
KW - DNA methylation
KW - epigenome-wide association study
KW - metals
KW - pathway enrichment
UR - http://www.scopus.com/inward/record.url?scp=85011301697&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011301697&partnerID=8YFLogxK
U2 - 10.1080/15592294.2016.1271853
DO - 10.1080/15592294.2016.1271853
M3 - Article
C2 - 27982729
AN - SCOPUS:85011301697
SN - 1559-2294
VL - 12
SP - 139
EP - 148
JO - Epigenetics
JF - Epigenetics
IS - 2
ER -