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

Bauer M, Linsel G, Fink B, Offenberg K, Hahn AM, Sack U, Knaack H, Eszlinger M, Herberth G - Clin Epigenetics (2015)

Bottom Line: Within two independent cohorts, we confirmed the differentially expression of the GPR15 gene when smokers and non-smokers subjects are compared.Treatment of peripheral blood mononuclear cell (PBMC) cultures with aqueous cigarette smoke extract did not induce a higher proportion of this T cell subtype.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, 04318 Germany.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

GPR15 gene expression in whole blood versus frequency of GPR15 expressing T lymphocytes. Percentage of GPR15+ of CD3+ T cells (a) and of CD19+ B cells (b). Correlation coefficient from linear regression analysis
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Fig3: GPR15 gene expression in whole blood versus frequency of GPR15 expressing T lymphocytes. Percentage of GPR15+ of CD3+ T cells (a) and of CD19+ B cells (b). Correlation coefficient from linear regression analysis

Mentions: In the Replication Cohort, GPR15 gene expression as well as the frequency of GPR15+ lymphocytes among CD3+ T cells and CD19+ B cells were measured in white blood cells. The strongest correlation was found between GPR15 gene expression and the proportion of CD3+GPR15+ T cells (R2 = 0.72, p = 8.4−28). The amount of CD19+GPR15+ B cells was only marginally correlated with the GPR15 gene expression in WBC (R2 = 0.12, p = 5.0−4), Fig. 3.Fig. 3


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

Bauer M, Linsel G, Fink B, Offenberg K, Hahn AM, Sack U, Knaack H, Eszlinger M, Herberth G - Clin Epigenetics (2015)

GPR15 gene expression in whole blood versus frequency of GPR15 expressing T lymphocytes. Percentage of GPR15+ of CD3+ T cells (a) and of CD19+ B cells (b). Correlation coefficient from linear regression analysis
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4526203&req=5

Fig3: GPR15 gene expression in whole blood versus frequency of GPR15 expressing T lymphocytes. Percentage of GPR15+ of CD3+ T cells (a) and of CD19+ B cells (b). Correlation coefficient from linear regression analysis
Mentions: In the Replication Cohort, GPR15 gene expression as well as the frequency of GPR15+ lymphocytes among CD3+ T cells and CD19+ B cells were measured in white blood cells. The strongest correlation was found between GPR15 gene expression and the proportion of CD3+GPR15+ T cells (R2 = 0.72, p = 8.4−28). The amount of CD19+GPR15+ B cells was only marginally correlated with the GPR15 gene expression in WBC (R2 = 0.12, p = 5.0−4), Fig. 3.Fig. 3

Bottom Line: Within two independent cohorts, we confirmed the differentially expression of the GPR15 gene when smokers and non-smokers subjects are compared.Treatment of peripheral blood mononuclear cell (PBMC) cultures with aqueous cigarette smoke extract did not induce a higher proportion of this T cell subtype.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, 04318 Germany.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus