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Sci Rep. 2017 Feb 22;7:42870. doi: 10.1038/srep42870.

Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases.

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National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
Department of Biobank Research, and Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Sweden.
Nutrition Research, Department of Public Health and Clinical Medicine, Umeå University, Sweden.
The Institute for Cancer Research and Prevention, Italy.
Imperial College London, MRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, W2 1PG, UK.
Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, UK.


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.

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