PMID- 18628791 OWN - NLM STAT- MEDLINE DCOM- 20090107 LR - 20081121 IS - 1018-4813 (Print) IS - 1018-4813 (Linking) VI - 16 IP - 12 DP - 2008 Dec TI - Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project. PG - 1512-20 LID - 10.1038/ejhg.2008.127 [doi] AB - 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. FAU - Grisoni, Marie-Lise AU - Grisoni ML AD - INSERM, UMR_S 525, Paris, France. FAU - Proust, Carole AU - Proust C FAU - Alanne, Mervi AU - Alanne M FAU - DeSuremain, Maylis AU - DeSuremain M FAU - Salomaa, Veikko AU - Salomaa V FAU - Kuulasmaa, Kari AU - Kuulasmaa K FAU - Cambien, Francois AU - Cambien F FAU - Nicaud, Viviane AU - Nicaud V FAU - Stegmayr, Birgitta AU - Stegmayr B FAU - Virtamo, Jarmo AU - Virtamo J FAU - Shields, Denis AU - Shields D FAU - Kee, Frank AU - Kee F FAU - Tiret, Laurence AU - Tiret L FAU - Evans, Alun AU - Evans A FAU - Tregouet, David-Alexandre AU - Tregouet DA CN - MORGAM Project LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20080716 PL - England TA - Eur J Hum Genet JT - European journal of human genetics : EJHG JID - 9302235 RN - 0 (Interleukin-18) SB - IM MH - Cardiovascular Diseases/epidemiology/*genetics MH - Case-Control Studies MH - Cohort Studies MH - Computer Simulation MH - Genetics, Population/methods MH - Genome-Wide Association Study MH - Haplotypes MH - Humans MH - Interleukin-18/*genetics MH - *Polymorphism, Single Nucleotide MH - Regression Analysis MH - Sequence Tagged Sites MH - Smoking/epidemiology/genetics FIR - Salomaa, V IR - Salomaa V FIR - Juolevi, A IR - Juolevi A FIR - Vartiainen, E IR - Vartiainen E FIR - Jousilahti, P IR - Jousilahti P FIR - Virtamo, J IR - Virtamo J FIR - Kilpelainen, H IR - Kilpelainen H FIR - Virtanen, M IR - Virtanen M FIR - Kuulasmaa, K IR - Kuulasmaa K FIR - Cepaitis, Z IR - Cepaitis Z FIR - Haukijarvi, A IR - Haukijarvi A FIR - Joseph, B IR - Joseph B FIR - Karvanen, J IR - Karvanen J FIR - Kulathinal, S IR - Kulathinal S FIR - Niemela, M IR - Niemela M FIR - Saarela, O IR - Saarela O FIR - Peltonen, L IR - Peltonen L FIR - Perola, M IR - Perola M FIR - Silander, K IR - Silander K FIR - Alanne, M IR - Alanne M FIR - Laiho, P IR - Laiho P FIR - Kristiansson, K IR - Kristiansson K FIR - Ahonen, K IR - Ahonen K FIR - Ducimetiere, P IR - Ducimetiere P FIR - Bingham, A IR - Bingham A FIR - Arveiler, D IR - Arveiler D FIR - Haas, B IR - Haas B FIR - Wagner, A IR - Wagner A FIR - Ferrieres, J IR - Ferrieres J FIR - Ruidavets, J-B IR - Ruidavets JB FIR - Bongard, V IR - Bongard V FIR - Deckers, D IR - Deckers D FIR - Saulet, C IR - Saulet C FIR - Barrere, S IR - Barrere S FIR - Amouyel, P IR - Amouyel P FIR - Montaye, M IR - Montaye M FIR - Lemaire, B IR - Lemaire B FIR - Beauchant, S IR - Beauchant S FIR - Cottel, D IR - Cottel D FIR - Graux, C IR - Graux C FIR - Marecaux, N IR - Marecaux N FIR - Steclebout, C IR - Steclebout C FIR - Szeremeta, S IR - Szeremeta S FIR - Cambien, F IR - Cambien F FIR - Tiret, L IR - Tiret L FIR - Nicaud, V IR - Nicaud V FIR - Stegmayr, B IR - Stegmayr B FIR - Asplund, K IR - Asplund K FIR - Nasic, S IR - Nasic S FIR - Ronnberg, G IR - Ronnberg G FIR - Johansson, A IR - Johansson A FIR - Lundberg, V IR - Lundberg V FIR - Jagare-Westerberg, E IR - Jagare-Westerberg E FIR - Messner, T IR - Messner T FIR - Evans, A IR - Evans A FIR - Yarnell, J IR - Yarnell J FIR - Gardner, E IR - Gardner E FIR - Evans, A IR - Evans A FIR - Cashman, S IR - Cashman S FIR - Kee, F IR - Kee F FIR - Evans, A IR - Evans A FIR - Blankenberg, S IR - Blankenberg S FIR - Cambien, F IR - Cambien F FIR - Ferrario, M IR - Ferrario M FIR - Kuulasmaa, K IR - Kuulasmaa K FIR - Peltonen, L IR - Peltonen L FIR - Perola, M IR - Perola M FIR - Salomaa, V IR - Salomaa V FIR - Shields, D IR - Shields D FIR - Stegmayr, B IR - Stegmayr B FIR - Tunstall-Pedoe, H IR - Tunstall-Pedoe H FIR - Asplund, K IR - Asplund K EDAT- 2008/07/17 09:00 MHDA- 2009/01/08 09:00 CRDT- 2008/07/17 09:00 PHST- 2008/07/17 09:00 [pubmed] PHST- 2009/01/08 09:00 [medline] PHST- 2008/07/17 09:00 [entrez] AID - ejhg2008127 [pii] AID - 10.1038/ejhg.2008.127 [doi] PST - ppublish SO - Eur J Hum Genet. 2008 Dec;16(12):1512-20. doi: 10.1038/ejhg.2008.127. Epub 2008 Jul 16.