A varying T cell subtype explains apparent tobacco smoking induced single CpG hypomethylation in whole blood

作者：Bauer Mario; Linsel Gunter; Fink Beate; Offenberg Kirsten; Hahn Anne Maria; Sack Ulrich; Knaack Heike; Eszlinger Markus; Herberth Gunda^*

来源：Clinical Epigenetics, 2015, 7(1): 81.

DOI：10.1186/s13148-015-0113-1

• DNA methylation
• CpG
• GPR15
• Tobacco smoking
• Blood
• EWAS cell composition

Background: Many recent epigenetic studies report that cigarette smoking reduces DNA methylation in whole blood at the single CpG site cg19859270 within the GPR15 gene.
Results: Within two independent cohorts, we confirmed the differentially expression of the GPR15 gene when smokers and non-smokers subjects are compared. By validating the GPR15 protein expression at the cellular level, we found that the observed decreased methylation at this site in white blood cells (WBC) of smokers is mainly caused by the high proportion of CD3+GPR15+ expressing T cells in peripheral blood. In current smokers, the percentage of GPR15+ cells among CD3+ T cells in peripheral blood is significantly higher (15.5 +/- 7.2 %, mean +/- standard deviation) compared to non-smokers (3.7 +/- 1.6 %). Treatment of peripheral blood mononuclear cell (PBMC) cultures with aqueous cigarette smoke extract did not induce a higher proportion of this T cell subtype.
Conclusions: Our results underline that DNA hypomethylation at cg19859270 site, observed in WBCs of smokers, did not arise by direct effect of tobacco smoking compounds on methylation of DNA but rather by the enrichment of a tobacco-smoking-induced lymphocyte population in the peripheral blood.

• 出版日期2015-8-6