Interleukin 1 gene cluster, myocardial infarction at young age and inflammatory response of human mononuclear cells

Maria Carmela Latella, Monica De Gaetano, Augusto Di Castelnuovo, Emanuela Napoleone, Roberto Lorenzet, Marinella Gattone, Pantaleo Giannuzzi, John Rogus, Kenneth Huttner, Maria Benedetta Donati, Licia Iacoviello

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 0.400.95), p 0.01; OR 0.69 (95 CI 0.510.92), p 0.03, respectively]. Haplotype-pair A2A2 showed significant reduction in the risk of MI [OR 0.38 (95 CI 0.180.81); 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 A2A4 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.

Original languageEnglish
Pages (from-to)203-219
Number of pages17
JournalImmunological Investigations
Volume38
Issue number3-4
DOIs
Publication statusPublished - 2009

Fingerprint

Interleukins
Multigene Family
Interleukin-1
Haplotypes
Myocardial Infarction
varespladib methyl
Single Nucleotide Polymorphism
Lipopolysaccharides
Blood Cells
Multivariate Analysis
Coagulants
Population Control
Thromboplastin
Risk Reduction Behavior
Interleukin-1beta
Genes
Healthy Volunteers
Genotype

Keywords

  • Inflammation
  • Interleukin-1 gene cluster
  • Juvenile myocardial infarction
  • Tissue factor

ASJC Scopus subject areas

  • Immunology

Cite this

Interleukin 1 gene cluster, myocardial infarction at young age and inflammatory response of human mononuclear cells. / Latella, Maria Carmela; De Gaetano, Monica; Di Castelnuovo, Augusto; Napoleone, Emanuela; Lorenzet, Roberto; Gattone, Marinella; Giannuzzi, Pantaleo; Rogus, John; Huttner, Kenneth; Donati, Maria Benedetta; Iacoviello, Licia.

In: Immunological Investigations, Vol. 38, No. 3-4, 2009, p. 203-219.

Research output: Contribution to journalArticle

Latella, Maria Carmela ; De Gaetano, Monica ; Di Castelnuovo, Augusto ; Napoleone, Emanuela ; Lorenzet, Roberto ; Gattone, Marinella ; Giannuzzi, Pantaleo ; Rogus, John ; Huttner, Kenneth ; Donati, Maria Benedetta ; Iacoviello, Licia. / Interleukin 1 gene cluster, myocardial infarction at young age and inflammatory response of human mononuclear cells. In: Immunological Investigations. 2009 ; Vol. 38, No. 3-4. pp. 203-219.
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AU - Latella, Maria Carmela

AU - De Gaetano, Monica

AU - Di Castelnuovo, Augusto

AU - Napoleone, Emanuela

AU - Lorenzet, Roberto

AU - Gattone, Marinella

AU - Giannuzzi, Pantaleo

AU - Rogus, John

AU - Huttner, Kenneth

AU - Donati, Maria Benedetta

AU - Iacoviello, Licia

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N2 - 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 0.400.95), p 0.01; OR 0.69 (95 CI 0.510.92), p 0.03, respectively]. Haplotype-pair A2A2 showed significant reduction in the risk of MI [OR 0.38 (95 CI 0.180.81); 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 A2A4 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.

AB - 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 0.400.95), p 0.01; OR 0.69 (95 CI 0.510.92), p 0.03, respectively]. Haplotype-pair A2A2 showed significant reduction in the risk of MI [OR 0.38 (95 CI 0.180.81); 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 A2A4 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.

KW - Inflammation

KW - Interleukin-1 gene cluster

KW - Juvenile myocardial infarction

KW - Tissue factor

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