title: Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project.
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.
authors.affiliation: INSERM, UMR_S 525, Paris, France.
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Grisoni
authors.forename: Carole
authors.initials: C
authors.lastname: Proust
authors.forename: Mervi
authors.initials: M
authors.lastname: Alanne
authors.forename: Maylis
authors.initials: M
authors.lastname: DeSuremain
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Kari
authors.initials: K
authors.lastname: Kuulasmaa
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Birgitta
authors.initials: B
authors.lastname: Stegmayr
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Denis
authors.initials: D
authors.lastname: Shields
authors.forename: Frank
authors.initials: F
authors.lastname: Kee
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Tregouet
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003198:Computer Simulation; D005828:Genetics, Population / Q000379:methods; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D016324:Sequence Tagged Sites; D012907:Smoking / Q000453:epidemiology / Q000235:genetics
chemical_list: D020382:Interleukin-18