Interleukin 1 gene cluster, myocardial infarction at young age and inflammatory response of human mononuclear cells.
The objective was to investigate whether genotypes, haplotypes and haplotype-pairs of interleukin (IL) gene cluster are associated with risk of Myocardial Infarction (MI) at young age and with the release of IL-1B and expression of tissue factor pro-coagulant activity (TFPCA), after stimulation in vitro with lipopolysaccharide (LPS) of human peripheral blood mononuclear cells (PBMCs). Patients with MI at young age, frequency-matched for age, sex and recruitment centre, with healthy population-based controls and PBMCs from healthy volunteers were studied. Five single nucleotide polymorphisms (SNPs), identifying two haplotype-blocks, in IL-1B gene and one SNP in IL-1A and IL-RA genes were genotyped. In multivariate analyses, haplotype A2 (122) and A4 (112) were associated with decreased risk of MI [OR = 0.62 (95% CI = 0.40-0.95), p = 0.01; OR = 0.69 (95% CI = 0.51-0.92), p = 0.03, respectively]. Haplotype-pair A2/A2 showed significant reduction in the risk of MI [OR = 0.38 (95% CI = 0.18-0.81); p = 0.01]. Haplotype A2 and A4 were associated with lower levels of IL-1B (respectively p = 0.01; p = 0.04, multivariate analysis) and haplotype-pair A2/A4 showed decreased levels of IL-1beta (p = 0.02). No association was found between block "B" IL-1B haplotypes or IL-1A and IL-RA polymorphisms and risk of MI. IL-1B haplotypes influence the inflammatory response of human mononuclear cells to LPS and affect the risk of MI at young age.
Latella
Maria Carmela
MC
John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.
de Gaetano
Monica
M
Di Castelnuovo
Augusto
A
Napoleone
Emanuela
E
Lorenzet
Roberto
R
Gattone
Marinella
M
Giannuzzi
Pantaleo
P
Rogus
John
J
Huttner
Kenneth
K
Donati
Maria Benedetta
MB
Iacoviello
Licia
L
D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics
D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I