title: Interleukin 1 gene cluster, myocardial infarction at young age and inflammatory response of human mononuclear cells.
abstract: 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.
authors.affiliation: John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Latella
authors.forename: Monica
authors.initials: M
authors.lastname: de Gaetano
authors.forename: Augusto
authors.initials: A
authors.lastname: Di Castelnuovo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Napoleone
authors.forename: Roberto
authors.initials: R
authors.lastname: Lorenzet
authors.forename: Marinella
authors.initials: M
authors.lastname: Gattone
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Giannuzzi
authors.forename: John
authors.initials: J
authors.lastname: Rogus
authors.forename: Kenneth
authors.initials: K
authors.lastname: Huttner
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Donati
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
mesh_terms: 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
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I