4.5 Article

Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA)

Journal

EPIGENETICS
Volume 12, Issue 12, Pages 1092-1100

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15592294.2017.1403692

Keywords

CD14+monocyte; Cigarette; cotinine; DNA methylation; gene expression; smoking; tobacco

Funding

  1. National Heart, Lung, And Blood Institute (NHLBI) of the National Institutes of Health (NIH) [P50HL120163]
  2. Intramural Research Program of the National Institute of Environmental Health Sciences
  3. NIEHS [ZO1-ES100475, Z01 ES046008]
  4. NHLBI [R01HL101250, R01 DK103531-01, R01 HL135009-01]
  5. MESA Lung Study [R01-HL077612, R01-HL093081]
  6. US Environmental Protection Agency [RD831697]
  7. MESA investigators
  8. [N01-HC-95159]
  9. [N01-HC-95160]
  10. [N01-HC-95161]
  11. [N01-HC-95162]
  12. [N01-HC-95163]
  13. [N01-HC-95164]
  14. [N01-HC-95165]
  15. [N01-HC-95166]
  16. [N01-HC-95167]
  17. [N01-HC-95168]
  18. [N01-HC-95169]
  19. [UL1-TR-001079]
  20. [UL1-TR-000040]
  21. [DK063491]

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Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+ purified monocyte samples from 934 participants of the community-based Multi-Ethnic Study of Atherosclerosis (MESA). Urine cotinine levels were measured using an immunoassay. DNA methylation and gene expression were measured with microarrays. Multivariate linear regression was used to test for associations adjusting for age, sex, race/ethnicity, education, and study site. Urine cotinine levels were associated with methylation of 176 CpGs [false discovery rate (FDR)<0.01]. Four CpGs not previously identified by studies of non-purified blood samples nominally replicated (P value<0.05) with plasma cotinine-associated methylation in 128 independent monocyte samples. Urine cotinine levels associated with expression of 12 genes (FDR<0.01), including increased expression of P2RY6 (Beta +/- standard error = 0.078 +/- 0.008, P = 1.99 x 10(-22)), a gene previously identified to be involved in the release of pro-inflammatory cytokines. No cotinine-associated (FDR<0.01) methylation profiles significantly (FDR<0.01) correlated with cotinine-associated (FDR<0.01) gene expression profiles. In conclusion, our findings i) identify potential monocyte-specific smoking-associated methylation patterns and ii) suggest that alterations in methylation may not be a main mechanism regulating gene expression in monocytes in response to cigarette smoking.

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