A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease |
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| Authors: | Michael V. Holmes,Ruth Frikke-Schmidt,Daniela Melis,Robert Luben,Folkert W. Asselbergs,Jolanda M.A. Boer,Jackie Cooper,Jutta Palmen,Pia Horvat,Jorgen Engmann,Ka-Wah Li,N. Charlotte Onland-Moret,Marten H. Hofker,Meena Kumari,Brendan J. Keating,Jaroslav A. Hubacek,Vera Adamkova,Ruzena Kubinova,Martin Bobak,Kay-Tee Khaw,Bø rge G. Nordestgaard,Nick Wareham,Steve E. Humphries,Claudia Langenberg,Anne Tybjaerg-Hansen,Philippa J. Talmud |
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| Affiliation: | 1. Department of Surgery, Division of Transplantation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;2. Department of Epidemiology & Public Health, University College London, London, UK;3. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;4. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark;5. The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark;6. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;g Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK;h Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK;i Department of Cardiology, Division Heart & Lungs, University Medical Center, Utrecht, The Netherlands;j Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands;k Institute of Cardiovascular Science, faculty of Population Health Sciences, University College London, London, United Kingdom;l Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands;m Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands;n Department of Pediatrics, Molecular Genetics, University Medical Center Groningen and Groningen University, Groningen, The Netherlands;o Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague 4, 14021, Czech Republic;p National Institute of Public Health, Srobarova 48, 10042 Prague, Czech Republic;q Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark;r MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, UK |
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| Abstract: | BackgroundConflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).Methods and resultsWe searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test.In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.ConclusionsIn the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD. |
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| Keywords: | APOE genotype Smoking Coronary heart disease Gene&ndash environment interaction |
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