Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein.
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 (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.
Vickers
Mark A
MA
Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK.
Green
Fiona R
FR
Terry
Catherine
C
Mayosi
Bongani M
BM
Julier
Cecile
C
Lathrop
Mark
M
Ratcliffe
Peter J
PJ
Watkins
Hugh C
HC
Keavney
Bernard
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values
D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein