Abstract
Interleukin-18 (IL-18) is a key inflammatory molecule suspected of being involved in the etiology of cardiovascular diseases (CVD). Five single nucleotide polymorphisms (SNPs) capturing the common genetic variation of the IL-18 gene (tag SNPs) were genotyped in five European prospective CVD cohorts including 1933 cases and 1938 non-cases as part of the MORGAM Project. Not a single SNP was found associated with CVD. However, a significant (P=0.002) gene–smoking interaction was observed. In smokers, the −105T allele was more frequent in cases than in non-cases (0.29 vs 0.25) and associated with an increased risk of disease (odds ratio (OR)=1.25 (1.07–1.45), P=0.005), whereas the inverse relationship tended to be observed in non-smokers (OR=0.90 (0.78–1.02), P=0.131). The gene–smoking interaction was broadly homogenous across the cohorts and was also observed through haplotype analyses. In conclusion, using the concerted effort of several European prospective CVD cohorts, we are able to show that one IL-18 tag SNP interacts with smoking to modulate the risk of developing CVD.
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Acknowledgements
The research was supported by the MORGAM Project grant under the Biomed 2 Programme, by the GenomEUtwin Project grant under the Programme ‘Quality of Life and Management of the Living Resources’ of fifth Framework Programme (no. QLG2-CT-2002-01254) and by the European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413.
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Supplementary Information accompanies the paper on European Journal of Human Genetics website (http://www.nature.com/ejhg)
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MORGAM Website: http://www.ktl.fi/publications/morgam/index.html
Sites and key personnel of contributing MORGAM centers:
Finland
FINRISK, National Public Health Institute, Helsinki: V Salomaa (principal investigator), A Juolevi, E Vartiainen, P Jousilahti; ATBC, National Public Health Institute, Helsinki: J Virtamo (principal investigator), H Kilpeläinen, M Virtanen; MORGAM Data Centre, National Public Health Institute, Helsinki: K Kuulasmaa (head), Z Cepaitis, A Haukijärvi, B Joseph, J Karvanen, S Kulathinal, M Niemelä, O Saarela; MORGAM Central Laboratory, National Public Health Institute, Helsinki: L Peltonen (responsíble person), M Perola, K Silander, M Alanne, P Laiho, K Kristiansson, K Ahonen.
France
National Coordinating Centre, National Institute of Health and Medical Research (U258), Paris: P Ducimetière (national coordinator), A Bingham; PRIME/Strasbourg, Department of Epidemiology and Public Health, Louis Pasteur University, Faculty of Medicine, Strasbourg: D Arveiler (principal investigator), B Haas, A Wagner; PRIME/Toulouse, Department of Epidemiology, Toulouse University School of Medicine, Toulouse: J Ferrières (principal investigator), J-B Ruidavets, V Bongard, D Deckers, C Saulet, S Barrere; PRIME/Lille, Department of Epidemiology and Public Health, Pasteur Institute of Lille: P Amouyel (principal investigator), M Montaye, B Lemaire, S Beauchant, D Cottel, C Graux, N Marecaux, C Steclebout, S Szeremeta; MORGAM Laboratory, INSERM U525, Paris: F Cambien (responsible person), L Tiret, V Nicaud.
Sweden
Northern Sweden, Umeå University Hospital, Department of Medicine, Umeå: B Stegmayr (principal investigator), K Asplund (former principal investigator), S Nasic, G Rönnberg, Å Johansson, V Lundberg, E Jägare-Westerberg, T Messner.
United Kingdom
PRIME/Belfast, Queen's University Belfast, Belfast, Northern Ireland: A Evans (principal investigator), J Yarnell, E Gardner; MORGAM Coordinating Centre, Queen's University Belfast, Belfast, Northern Ireland: A Evans (MORGAM coordinator), S Cashman, F Kee.
MORGAM Management Group: A Evans (chair), S Blankenberg (Mainz, Germany), F Cambien, M Ferrario (Varese, Italy), K Kuulasmaa, L Peltonen, M Perola, V Salomaa, D Shields (Dublin, Ireland), B Stegmayr, H Tunstall-Pedoe (Dundee, Scotland), K Asplund (honorary consultant, Stockholm Sweden).
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Grisoni, ML., Proust, C., Alanne, M. et al. Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project. Eur J Hum Genet 16, 1512–1520 (2008). https://doi.org/10.1038/ejhg.2008.127
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DOI: https://doi.org/10.1038/ejhg.2008.127
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