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Thromb Haemost 2005; 94(03): 646-650
DOI: 10.1160/TH05-03-0203
Cell Signalling and Vessel Remodelling
Schattauer GmbH

Interleukin-1 gene cluster variants and abdominal aortic aneurysms

A matched case control study
Rodrig Marculescu
1   Departments of Medical and Chemical laboratory Diagnostics
,
Gottfried Sodeck
2   Emergency Medicine
,
Hans Domanovits
2   Emergency Medicine
,
Gerhard Hobusch
1   Departments of Medical and Chemical laboratory Diagnostics
,
Markus Exner
1   Departments of Medical and Chemical laboratory Diagnostics
,
Harald Heinzl
3   Core Unit for Medical Statistics and Informatics
,
Kurt Huber
,
Christine Mannhalter
1   Departments of Medical and Chemical laboratory Diagnostics
,
Erich Minar
1   Departments of Medical and Chemical laboratory Diagnostics
5   Angiology, Vienna Medical University, Vienna, Austria
,
Oswald Wagner
1   Departments of Medical and Chemical laboratory Diagnostics
,
Martin Schillinger
5   Angiology, Vienna Medical University, Vienna, Austria
› Author Affiliations Grant support: This study was supported by grants from the “Hans und Blanca Moser-Stiftung zur Förderung der Ausbildung von Krebs- und Herzspezialisten” and the “Österreichische Kardiologische Gesellschaft” to Dr. Rodrig Marculescu.
Further Information

Publication History

Received: 24 March 2005

Accepted after major revision: 29 May 2005

Publication Date:
07 December 2017 (online)

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Summary

Inflammation is a key factor in the pathogenesis of abdominal aortic aneurysms (AAA). Interleukin 1 (IL-1), a fundamental regulator of the inflammatory cascade, has been shown to be involved in this process. Several functional polymorphisms in the IL-1 gene cluster are known. In this matched case-control study, we investigated a potential association between six genetic variants in IL-1 and IL-1 receptor antagonist (IL-1 RN) withAAA. We enrolled 405 individuals, 135 consecutive patients with AAA were individually age- and sex-matched to 270 patients with coronary artery disease (CAD). Traditional cardiovascular risk factors and IL-1 genotypes were determined, and the distribution of six single nucleotide polymorphisms were compared between patients and controls by multivariable conditional logistic regression analysis: IL-1A (-889) C>T, IL-1A (+4845) G>T, IL-1B (-511) C>T, IL-1B (-31) C>T, IL-1B (+3954) C>T and IL-1RN (+2018) C>T. IL-1A (-889) C>T and IL-1A (+4845) G>T (kappa 0.98, 95% CI 0.96 to 1.00), and IL-1B (-511) C>T and IL-1B (-31) C>T (kappa 0.98, 95% CI 0.96 to 1.00) were closely linked, therefore IL-1A (-889) C>T and IL-1B (-31) C>T were not considered for further analyses. None of the 4 remaining polymorphisms showed a significant association with AAA: IL-1RN (+2018) C>T (p=0.061), IL-1B (+3954) C>T (p=0.51), IL-1B (-511) C>T (p=0.61) and IL-1A (+4845) G>T (p=0.81). No significant first-degree interactions between the genetic variants andAAA were detected. In conclusion, these six genetic variants in the interleukin-1 gene cluster do not seem to play a clinically relevant role in the pathogenesis of AAA, although we cannot rule out the existence of higher degree gene-gene or gene-environment interactions.

Keywords

Abdominal aortic aneurysm - interleukin 1 - inflammation
 

  • References

  • 1 Freestone T, Turner RJ, Coady A. et al. Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm.. Arterioscler Thromb Vasc Biol 1995; 15: 1145-51.
    CrossrefPubMedGoogle Scholar
  • 2 Shah PK. Inflammation, metalloproteinases, and increased proteolysis: an emerging pathophysiological paradigm in aortic aneurysm.. Circulation 1997; 96: 2115-7.
    CrossrefPubMedGoogle Scholar
  • 3 Juvonen J, Surcel HM, Satta J. et al. Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm.. Arterioscler Thromb Vasc Biol 1997; 17: 2843-7.
    CrossrefPubMedGoogle Scholar
  • 4 Geng YJ, Wu Q, Muszynski M. et al. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factoralpha, and interleukin-1 beta.. Arterioscler Thromb Vasc Biol 1996; 16: 19-27.
    CrossrefPubMedGoogle Scholar
  • 5 Keen RR, Nolan KD, Cipollone M. et al. Interleukin- 1 beta induces differential gene expression in aortic smooth muscle cells.. J Vasc Surg 1994; 20: 774-84.
    CrossrefPubMedGoogle Scholar
  • 6 El-Omar EM, Carrington M, Chow WH. et al. Interleukin- 1 polymorphisms associated with increased risk of gastric cancer.. Nature 2000; 404: 398-402.
    CrossrefPubMedGoogle Scholar
  • 7 Hamajima N, Matsuo K, Saito T. et al. Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection.. Jpn J Cancer Res 2001; 92: 383-9.
    CrossrefPubMedGoogle Scholar
  • 8 Kornman KS, Crane A, Wang HY. et al. The interleukin- 1 genotype as a severity factor in adult periodontal disease.. J Clin Periodont 1997; 24: 72-7.
    CrossrefPubMedGoogle Scholar
  • 9 Diehl SR, Wang Y, Brooks CN. et al. Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis.. J Periodont 1999; 70: 418-30.
    CrossrefPubMedGoogle Scholar
  • 10 Du Y, Dodel RC, Eastwood BJ. et al. Association of an interleukin1-alpha polymorphism with Alzheimer´s disease.. Neurology 2000; 55: 480-4.
    CrossrefPubMedGoogle Scholar
  • 11 Grimaldi LME, Casadei VM, Ferri C. et al. Association of early-onset Alzheimer´s disease with an interleukin- 1-alpha polymorphism.. Ann Neurol 2000; 47: 361-5.
    CrossrefPubMedGoogle Scholar
  • 12 Marculescu R, Mlekusch W, Exner M. et al. Interleukin- 1 cluster combined genotype and restenosis after balloon angioplasty.. Thromb Haemost 2003; 90: 491-500.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Francis SE, Camp NJ, Dewberry RM. et al. Interleukin- 1 receptor antagonist gene polymorphism and coronary artery disease.. Circulation 1999; 99: 861-6.
    CrossrefPubMedGoogle Scholar
  • 14 Momiyama Y, Hirano R, Taniguchi H. et al. Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection.. J Am Coll Cardiol 2001; 38: 712-7.
    CrossrefPubMedGoogle Scholar
  • 15 Marculescu R, Endler G, Schillinger M. et al. Interleukin- 1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes.. Diabetes 2002; 51: 3582-5.
    CrossrefPubMedGoogle Scholar
  • 16 Kastrati A, Koch W, Berger PB. et al. Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting.. J Am Coll Cardiol 2000; 36: 2168-73.
    CrossrefPubMedGoogle Scholar
  • 17 Francis SE, Camp NJ, Burton AJ. et al. Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty.. Heart 2001; 86: 336-40.
    CrossrefPubMedGoogle Scholar
  • 18 Rust S, Funke H, Assmann G. Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection.. Nucleic Acids Res 1993; 21: 3623-9.
    CrossrefPubMedGoogle Scholar
  • 19 Hurme M, Santtila S. IL-1 receptor antagonist (IL- 1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes.. Eur J Immunol 1998; 28: 2598-602.
    CrossrefPubMedGoogle Scholar
  • 20 Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro.. Scand J Immunol 1998; 47: 195-8.
    CrossrefPubMedGoogle Scholar
  • 21 Dewberry R, Holden H, Crossman D. et al. Interleukin- 1 receptor antagonist expression in human endothelial cells and atherosclerosis.. Arterioscler Thromb Vasc Biol 2000; 20: 2394-400.
    CrossrefPubMedGoogle Scholar
  • 22 Johansen K, Koepsell T. Familial tendency for abdominal aortic aneurysms.. JAMA. 1986; 256: 1934-6.
    CrossrefPubMedGoogle Scholar
  • 23 Darling RC, III Brewster DC, Darling RC. et al. Are familial abdominal aortic aneurysms different?. J Vasc Surg 1989; 10: 39-43.
    CrossrefPubMedGoogle Scholar
  • 24 Webster MW, Ferrell RE, St Jean PL. et al. Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm.. J Vasc Surg 1991; 13: 9-13.
    CrossrefPubMedGoogle Scholar
  • 25 Schillinger M, Exner M, Mlekusch W. et al. Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic aneurysm.. Thromb Res 2002; 106: 131-6.
    CrossrefPubMedGoogle Scholar
  • 26 Bown MJ, Burton PR, Horsburgh T. et al. The role of cytokine gene polymorphisms in the pathogenesis of abdominal aortic aneurysms: a case-control study.. J Vasc Surg 2003; 37: 999-1005.
    CrossrefPubMedGoogle Scholar
  • 27 Jones KG, Brull DJ, Brown LC. et al. Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.. Circulation 2001; 103: 2260-5.
    CrossrefPubMedGoogle Scholar