Effects of smoking and smoking cessation on human serum metabolite profile: results from the KORA cohort study
1 Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany
2 Else Kroener-Fresenius-Center for Nutritional Medicine, University Hospital, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, Munich, 81675, Germany
3 Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yue Yang Road 320, Shanghai, 200031, China
4 University of Chinese Academy of Sciences, Yuquanlu 19A, Beijing, 100049, China
5 Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany
6 Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany
7 Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Moorenstr. 5, Düsseldorf, 40225, Germany
8 Institute of Epidemiology I, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany
9 Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Marchioninistr. 15, Munich, 81377, Germany
10 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald; Ernst-Moritz-Arndt University, Ferdinand-Sauerbruch-Straße, Greifswald, 17475, Germany
11 Institute of Epidemiology II, Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany
12 Department of Psychosomatic Medicine and Psychotherapy, University Hospital, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, Munich, 81675, Germany
13 Department of Mathematics, Technische Universität München, Boltzmannstraße 3, Garching, 85748, Germany
14 Faculty of Biology, Ludwig-Maximilians-Universität, Großhaderner Straße 2-4, Planegg-Martinsried, 82152, Germany
15 Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar (WCMC-Q), PO Box 24144, Doha, Qatar
16 Chair of Experimental Genetics, Technische Universität München, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany
17 Hannover Unified Biobank, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover, 30625, Germany
18 Harvard School of Public Health, Department of Environmental Health, 677 Huntington Avenue, Boston, 02115, USA
BMC Medicine 2013, 11:60 doi:10.1186/1741-7015-11-60Published: 4 March 2013
Metabolomics helps to identify links between environmental exposures and intermediate biomarkers of disturbed pathways. We previously reported variations in phosphatidylcholines in male smokers compared with non-smokers in a cross-sectional pilot study with a small sample size, but knowledge of the reversibility of smoking effects on metabolite profiles is limited. Here, we extend our metabolomics study with a large prospective study including female smokers and quitters.
Using targeted metabolomics approach, we quantified 140 metabolite concentrations for 1,241 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) human cohort at two time points: baseline survey conducted between 1999 and 2001 and follow-up after seven years. Metabolite profiles were compared among groups of current smokers, former smokers and never smokers, and were further assessed for their reversibility after smoking cessation. Changes in metabolite concentrations from baseline to the follow-up were investigated in a longitudinal analysis comparing current smokers, never smokers and smoking quitters, who were current smokers at baseline but former smokers by the time of follow-up. In addition, we constructed protein-metabolite networks with smoking-related genes and metabolites.
We identified 21 smoking-related metabolites in the baseline investigation (18 in men and six in women, with three overlaps) enriched in amino acid and lipid pathways, which were significantly different between current smokers and never smokers. Moreover, 19 out of the 21 metabolites were found to be reversible in former smokers. In the follow-up study, 13 reversible metabolites in men were measured, of which 10 were confirmed to be reversible in male quitters. Protein-metabolite networks are proposed to explain the consistent reversibility of smoking effects on metabolites.
We showed that smoking-related changes in human serum metabolites are reversible after smoking cessation, consistent with the known cardiovascular risk reduction. The metabolites identified may serve as potential biomarkers to evaluate the status of smoking cessation and characterize smoking-related diseases.