C-reactive protein genetics is associated with carotid artery compliance in men in the cardiovascular risk in young Finns study

¹C Eklund, ²M Kivimäki, ³Md S Islam, ⁴M Juonala, ⁵M Kähönen, ⁶J Marniemi, ⁷T Lehtimäki, ⁸J Viikari, ⁸OT Raitakari, ⁹M Hurme
¹Departement of Microbiology and Immunology, University of Tampere Medical School, Tampere, Finland, ²Department of Epidemiology and Public Health, University College London, London, United Kingdom and Finnish Institute of Occupational Health, Helsinki, Finland, ³Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Finland and The George Institute for International Health, Royal Prince Alfred Hospital, Sydney, Australia, ⁴Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, ⁵Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland, ⁶Department of Health and Functional Capacity, National Public Health Institute, Turku, Finland, ⁷Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Tampere, Finland, ⁸Department of Clinical Physiology, University of Turku, Turku, Finland, ⁹Department of Microbiology and Immunology, Tampere University Hospital and Medical School, Tampere, Finland

Background Although C-reactive protein (CRP) is known to predict cardiovascular events, its status as a causal risk factor is still controversial. CRP gene single nucleotide polymorphisms (SNPs) have been shown to associate with CRP concentration, but no direct independent effect on early atherosclerotic changes has been demonstrated.

Aim We aimed to determine if CRP gene polymorphisms or haplotypes are associated with CRP concentration or carotid artery compliance (CAC), an indicator of subclinical atherosclerosis.

Methods We genotyped CRP gene polymorphisms -717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A and measured CRP concentration and CAC in 2283 young adults participating in the Cardiovascular Risk in Young Finns study.

Results A strong association was found between CRP genotypes and CRP concentration, which was also seen at the haplotype level. Linear regression analysis showed an independent effect of each SNP on CRP concentration after adjustment for risk factors, except for +1444 in males. Moreover, -286C>T>A, +1444C>T and +1846G>A were associated with CAC in males, but not in females. Men carrying the SNP -286 allele C had increased CAC after adjusting for risk factors.

Summary These data suggest that the presence of high producer CRP genotype is deleterious to carotid elasticity in men.