Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein

Mark Adrian Vickers, F. R. Green, B. M. Mayosi, M. Lathrop, PJ. Ratcliffe, HC. Watkins, B. Keavney, C. Terry, C. Julier

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225 Citations (Scopus)

Abstract

Objective: Baseline concentrations of plasma C-reactive protein (CRP) are associated with coronary heart disease. Interleukin-6 (IL-6) regulates CRP gene expression; a promoter polymorphism (-174G/C) of the JL-6 gene has been shown to influence IL-6 transcription but the relationship between genotype at this polymorphism and circulating levels of inflammatory markers remains unclear. We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism. Methods: We measured baseline plasma CRP and determined genotypes at the -174G/C polymorphism of the IL-6 gene in 588 members of 98 nuclear families. The heritability of plasma CRP and the association of plasma CRP with genotype were determined using variance components methods. Results: Baseline CRP levels were highly heritable (h(2) =0.39, P<0.0000001). Presence of the -174C allele was associated with higher baseline CRP levels, both in the whole population (P=0.01), and in the founders only (n=128, P=0.001). Family-based analyses confirmed the association (P=0.02) suggesting that it arises from chromosomal proximity or identity of the typed polymorphism with a genetic variant influencing baseline CRP levels. Conclusions: Baseline plasma CRP is a significantly heritable cardiovascular risk factor. Levels are associated with genotype at the -174G/C polymorphism of the IL-6 gene. (C) 2002 Elsevier Science B.V. All rights reserved.

Original languageEnglish
Pages (from-to)1029-1034
Number of pages5
JournalCardiovascular Research
Volume53
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • atherosclerosis
  • cytokines
  • epidemiology
  • infection/inflammation
  • sequence (DNA/RNA/prot)
  • CIRCULATING INTERLEUKIN-6
  • LINKAGE ANALYSIS
  • INFLAMMATION
  • DISEASE
  • DETERMINANTS
  • VARIABILITY
  • FIBRINOGEN
  • MARKERS
  • TRAITS
  • IL-6

Cite this

Vickers, M. A., Green, F. R., Mayosi, B. M., Lathrop, M., Ratcliffe, PJ., Watkins, HC., Keavney, B., Terry, C., & Julier, C. (2002). Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovascular Research, 53(4), 1029-1034. https://doi.org/10.1016/S0008-6363(01)00534-X