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Cardiovascular Research 2002 53(4):1029-1034; doi:10.1016/S0008-6363(01)00534-X
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

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

Mark A Vickersa,1, Fiona R Greenb,1, Catherine Terryb, Bongani M Mayosib, Cecile Julierc, Mark Lathropd, Peter J Ratcliffee, Hugh C Watkinsb and Bernard Keavneyf,*

aDepartment of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK
bDepartment of Cardiovascular Medicine, Oxford University, Oxford, UK
cInstitut Pasteur, Paris, France
dCentre National de Genotypage, Evry, France
eNuffield Department of Medicine, Oxford University, Oxford, UK
fInstitute of Human Genetics, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK

b.d.keavney{at}ncl.ac.uk

* Corresponding author. Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle-upon-Tyne NE1 3BZ, UK. Tel.: +44-191-2227-149; fax: +44-191-2220-723

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 IL-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 (h2=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.

KEYWORDS Atherosclerosis; Cytokines; Epidemiology; Infection/inflammation; Sequence (DNA/RNA/prot)

1 M.A.V. and F.R.G. contributed equally to this work.


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