title: Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases.
abstract: 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.
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Chatziioannou
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Georgiadis
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Dennie G
authors.initials: DG
authors.lastname: Hebels
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Liampa
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Valavanis
authors.affiliation: Department of Biobank Research, and Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Ingvar A
authors.initials: IA
authors.lastname: Bergdahl
authors.affiliation: Nutrition Research, Department of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.affiliation: The Institute for Cancer Research and Prevention, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Chadeau-Hyam
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Alexandros P
authors.initials: AP
authors.lastname: Siskos
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Hector
authors.initials: H
authors.lastname: Keun
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Botsivali
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Theo M C M
authors.initials: TM
authors.lastname: de Kok
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Almudena Espín
authors.initials: AE
authors.lastname: Pérez
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
authors.affiliation: 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.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Soterios A
authors.initials: SA
authors.lastname: Kyrtopoulos
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D014028:Tobacco Smoke Pollution