Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study

Stella Trompet, D. Pons, A. J M De Craen, P. Slagboom, J. Shepherd, G. J. Blauw, M. B. Murphy, S. M. Cobbe, E. L E M Bollen, B. M. Buckley, I. Ford, M. Hyland, A. Gaw, P. W. Macfarlane, C. J. Packard, J. Norrie, I. J. Perry, D. J. Stott, B. J. Sweeney, C. TwomeyR. G J Westendorp, J. W. Jukema

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), are implicated in the development of atherosclerosis. The role of anti-inflammatory cytokines, like IL-10, is largely unknown.We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene (4259AG, -1082GA, -592CA, and -2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associationswere assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the -592A variant allele) and risk of coronary events (P = 0.019). Moreover, analysis of separate SNPs found a significant association between -2849AA carriers with incident stroke (HR (95% CI) 1.50 (1.04-2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti-inflammatory cytokines may play an important role.

Original languageEnglish
Title of host publicationBiogerontology: Mechanisms and Interventions
EditorsSuresh I. S. Rattan, Serif Akman
Pages189-198
Number of pages10
Volume1100
DOIs
Publication statusPublished - Jun 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1100
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • Anti-inflammation
  • Atherosclerosis
  • Interleukin-10
  • Stroke

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