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Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes.

Publication ,  Journal Article
Su, D; Wang, X; Campbell, MR; Porter, DK; Pittman, GS; Bennett, BD; Wan, M; Englert, NA; Crowl, CL; Gimple, RN; Adamski, KN; Huang, Z ...
Published in: PLoS One
2016

Tobacco smoke exposure dramatically alters DNA methylation in blood cells and may mediate smoking-associated complex diseases through effects on immune cell function. However, knowledge of smoking effects in specific leukocyte subtypes is limited. To better characterize smoking-associated methylation changes in whole blood and leukocyte subtypes, we used Illumina 450K arrays and Reduced Representation Bisulfite Sequencing (RRBS) to assess genome-wide DNA methylation. Differential methylation analysis in whole blood DNA from 172 smokers and 81 nonsmokers revealed 738 CpGs, including 616 previously unreported CpGs, genome-wide significantly associated with current smoking (p <1.2x10-7, Bonferroni correction). Several CpGs (MTSS1, NKX6-2, BTG2) were associated with smoking duration among heavy smokers (>22 cigarettes/day, n = 86) which might relate to long-term heavy-smoking pathology. In purified leukocyte subtypes from an independent group of 20 smokers and 14 nonsmokers we further examined methylation and gene expression for selected genes among CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, and CD2+ T cells. In 10 smokers and 10 nonsmokers we used RRBS to fine map differential methylation in CD4+ T cells, CD8+ T cells, CD14+, CD15+, CD19+, and CD56+ natural killer cells. Distinct cell-type differences in smoking-associated methylation and gene expression were identified. AHRR (cg05575921), ALPPL2 (cg21566642), GFI1 (cg09935388), IER3 (cg06126421) and F2RL3 (cg03636183) showed a distinct pattern of significant smoking-associated methylation differences across cell types: granulocytes> monocytes>> B cells. In contrast GPR15 (cg19859270) was highly significant in T and B cells and ITGAL (cg09099830) significant only in T cells. Numerous other CpGs displayed distinctive cell-type responses to tobacco smoke exposure that were not apparent in whole blood DNA. Assessing the overlap between these CpG sites and differential methylated regions (DMRs) with RRBS in 6 cell types, we confirmed cell-type specificity in the context of DMRs. We identified new CpGs associated with current smoking, pack-years, duration, and revealed unique profiles of smoking-associated DNA methylation and gene expression among immune cell types, providing potential clues to hematopoietic lineage-specific effects in disease etiology.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

12

Start / End Page

e0166486

Location

United States

Related Subject Headings

  • Young Adult
  • Transcription Factors
  • T-Lymphocytes
  • Smoking
  • Sequence Analysis, DNA
  • Reverse Transcriptase Polymerase Chain Reaction
  • Repressor Proteins
  • Receptors, Thrombin
  • Monocytes
  • Middle Aged
 

Citation

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Su, D., Wang, X., Campbell, M. R., Porter, D. K., Pittman, G. S., Bennett, B. D., … Bell, D. A. (2016). Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes. PLoS One, 11(12), e0166486. https://doi.org/10.1371/journal.pone.0166486
Su, Dan, Xuting Wang, Michelle R. Campbell, Devin K. Porter, Gary S. Pittman, Brian D. Bennett, Ma Wan, et al. “Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes.PLoS One 11, no. 12 (2016): e0166486. https://doi.org/10.1371/journal.pone.0166486.
Su D, Wang X, Campbell MR, Porter DK, Pittman GS, Bennett BD, et al. Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes. PLoS One. 2016;11(12):e0166486.
Su, Dan, et al. “Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes.PLoS One, vol. 11, no. 12, 2016, p. e0166486. Pubmed, doi:10.1371/journal.pone.0166486.
Su D, Wang X, Campbell MR, Porter DK, Pittman GS, Bennett BD, Wan M, Englert NA, Crowl CL, Gimple RN, Adamski KN, Huang Z, Murphy SK, Bell DA. Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes. PLoS One. 2016;11(12):e0166486.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

12

Start / End Page

e0166486

Location

United States

Related Subject Headings

  • Young Adult
  • Transcription Factors
  • T-Lymphocytes
  • Smoking
  • Sequence Analysis, DNA
  • Reverse Transcriptase Polymerase Chain Reaction
  • Repressor Proteins
  • Receptors, Thrombin
  • Monocytes
  • Middle Aged