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Lookup NU author(s): Professor Bernard Keavney
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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.
Author(s): Keavney B; Vickers MA; Green FR; Terry C; Mayosi BM; Julier C; Lathrop M; Ratcliffe PJ; Watkins HC
Publication type: Article
Publication status: Published
Journal: Cardiovascular Research
Year: 2002
Volume: 53
Issue: 4
Pages: 1029-1034
ISSN (print): 0008-6363
ISSN (electronic): 1755-3245
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1016/S0008-6363(01)00534-X
DOI: 10.1016/S0008-6363(01)00534-X
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