Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project.
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.
Grisoni
Marie-Lise
ML
INSERM, UMR_S 525, Paris, France.
Proust
Carole
C
Alanne
Mervi
M
DeSuremain
Maylis
M
Salomaa
Veikko
V
Kuulasmaa
Kari
K
Cambien
François
F
Nicaud
Viviane
V
Stegmayr
Birgitta
B
Virtamo
Jarmo
J
Shields
Denis
D
Kee
Frank
F
Tiret
Laurence
L
Evans
Alun
A
Tregouet
David-Alexandre
DA
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
D020382:Interleukin-18