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.