A varying T cell subtype explains apparent tobacco smoking induced single CpG hypomethylation in whole blood.
A varying T cell subtype explains apparent tobacco smoking induced single CpG hypomethylation in whole blood.
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DOI：
10.1186/s13148-015-0113-1
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发表时间：
2015
影响因子：
5.7
通讯作者：
Herberth G
中科院分区：
文献类型：
--
作者：
Bauer M;Linsel G;Fink B;Offenberg K;Hahn AM;Sack U;Knaack H;Eszlinger M;Herberth G
最近的许多表观遗传学研究报道，吸烟会降低全血中GPR15基因内单个CpG位点cg19859270的DNA甲基化。在两个独立的队列中，我们证实了吸烟和不吸烟受试者GPR15基因表达的差异。通过在细胞水平上验证GPR15蛋白的表达，我们发现吸烟者白细胞（WBC）中该位点甲基化降低的主要原因是外周血中CD3+GPR15+表达的T细胞比例较高。在当前吸烟者中，外周血CD3+ T细胞中GPR15+细胞的百分比（15.5±7.2%，平均值±标准差）明显高于非吸烟者（3.7±1.6%）。用香烟烟雾水提取物处理外周血单核细胞（PBMC）培养物并没有诱导更高比例的这种T细胞亚型。我们的研究结果强调，在吸烟者的白细胞中观察到的cg19859270位点的DNA低甲基化不是由吸烟化合物对DNA甲基化的直接影响引起的，而是由吸烟诱导的外周血淋巴细胞群的富集引起的。本文的在线版本（doi:10.1186/s13148-015-0113-1）包含补充材料，可供授权用户使用。
Many recent epigenetic studies report that cigarette smoking reduces DNA methylation in whole blood at the single CpG site cg19859270 within the GPR15 gene. 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. 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. The online version of this article (doi:10.1186/s13148-015-0113-1) contains supplementary material, which is available to authorized users.