title: Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project.
abstract: BACKGROUND
  Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the IL18 gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, IL18R1 and IL18RAP, with the risk of developing CVD.
  
  
  METHODS
  Eleven tagging SNPs, 5 in IL18R1 and 6 in IL18RAP, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD.
  
  
  RESULTS
  We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 IL18 SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful.
  
  
  CONCLUSIONS
  Our analysis suggests that the variability of IL18R1 and IL18RAP genes are unlikely to contribute to modulate the risk of CVD.
authors.affiliation: INSERM, UMR_S 937, Paris, France. grisoni@chups.jussieu.fr
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: Per-Gunnar
authors.initials: PG
authors.lastname: Wiklund
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
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 / Q000235:genetics*; D015331:Cohort Studies; D005387:Finland; D005602:France; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics*; D053728:Interleukin-18 Receptor beta Subunit / Q000235:genetics*; D015810:Linkage Disequilibrium; D009660:Northern Ireland; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
chemical_list: C508572:IL18R1 protein, human; C115629:IL18RAP protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit