Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project.
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.
Grisoni
Marie-Lise
ML
INSERM, UMR_S 937, Paris, France. grisoni@chups.jussieu.fr
Proust
Carole
C
Alanne
Mervi
M
Desuremain
Maylis
M
Salomaa
Veikko
V
Kuulasmaa
Kari
K
Cambien
François
F
Nicaud
Viviane
V
Wiklund
Per-Gunnar
PG
Virtamo
Jarmo
J
Kee
Frank
F
Tiret
Laurence
L
Evans
Alun
A
Tregouet
David-Alexandre
DA
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
C508572:IL18R1 protein, human; C115629:IL18RAP protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit