Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases.
Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases.
复制标题
DOI：
10.1038/srep42870
复制
发表时间：
2017-02-22
影响因子：
4.6
通讯作者：
EnviroGenomarkers project consortium
中科院分区：
文献类型：
--
作者：
Chatziioannou A;Georgiadis P;Hebels DG;Liampa I;Valavanis I;Bergdahl IA;Johansson A;Palli D;Chadeau-Hyam M;Siskos AP;Keun H;Botsivali M;de Kok TM;Pérez AE;Kleinjans JC;Vineis P;Kyrtopoulos SA;EnviroGenomarkers project consortium
我们最近报道了明显健康的吸烟者血液白细胞中的差异基因表达和DNA甲基化谱，可以非常有效地预测已知与吸烟有因果关系的疾病和病症，这表明基于血液的人群组学谱可能有助于将环境暴露与潜在的健康影响联系起来。在这里，我们报告了吸烟对白细胞转录组学和表观遗传特征的性别特异性影响，鉴定了26个表达探针和92个CpG位点，几乎所有这些位点都只在女性吸烟者中受到影响。引人注目的是，这些特征与许多在心血管疾病发病机制中起关键作用的基因有关，特别是凝血酶信号，包括血小板上的凝血酶受体F2R(凝血因子II（凝血酶）受体；PAR1)和GP5（糖蛋白5），以及HMOX1（血红素加氧酶1）和BCL2L1 （bcl2样1）分别参与氧化应激和细胞凋亡的保护。这些结果与流行病学证据一致，即女性对烟草引起的心血管疾病易感性较高，并强调了基于血液的基因组分析在危害和风险评估中的潜力。
We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.