Polymorphism in the C-reactive protein (CRP) gene affects CRP levels in plasma and one early marker of atherosclerosis in men: The Health 2000 Survey

Abstract

Background. C-reactive protein (CRP) is an inflammatory protein that may play a role in the pathogenesis of cardiovascular disease (CVD). However, 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 not convincingly with early atherosclerotic changes. Objective. We assessed whether CRP genotypes or their haplotypes associate with plasma CRP levels or carotid artery intima-media thickness (IMT) or carotid artery elasticity (CAE) in a Finnish middle-aged study population. Methods. We genotyped CRP gene polymorphisms −717A>G (rs2794521), −286C>T>A (rs3091244), +1059G>C (rs1800947), +1444C>T (rs1130864) and +1846G>A (rs1205) and measured CRP concentration in a sub-population (N=1332, mean age 58.2 ± 8.0, women n=727 and men n=605) of a large Finnish cross-sectional health examination survey, The Health 2000 Study, carried out in 2000–2001. Results. Significant association (both sexes p<0.0001, women p=0.015 and men p=0.029) was found between CRP rs1800947 genotype and CRP concentration. Multivariate analysis showed an independent effect of the genotype on CRP concentration after adjustment for risk factors (women p=0.036 and men p=0.009). Similar associations were seen at the haplotype level in haplotype ACCCA where +1059 C-carriers had lower median CRP values than non-carriers (p=0.008). One CRP genotype (rs1130864) was associated with one CAE parameter in men but no association was observed between CRP genotypes and carotid artery IMT. Conclusions. CRP gene allelic variation is associated with CRP levels in both sexes and with one CAE parameter (SI) in men in a population-based Finnish cohort of middle-aged subjects.

Key Words::

• C-reactive protein genetics
• haplotypes
• single nucleotide polymorphism
• cardiovascular disease
• carotid artery intima-media thickness
• carotid artery elasticity

Acknowledgements

We thank the personnel in the field and the support organizations of the Health 2000 Survey at the National Public Health Institute of Finland. This study was financially support by the Medical Research Fund of the Tampere University Hospital, the Emil Aaltonen Foundation (T.L.), the Research Council for Health at the Academy of Finland, the Finnish Foundation for Cardiovascular Research and the Society for Clinical Biochemists.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.