title: 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.
authors.affiliation: Department of Clinical Chemistry, Centre for Laboratory Medicine Tampere University Hospital and University of Tampere, Finland. terhi.kettunen@elisanet.fi
authors.forename: Terhi
authors.initials: T
authors.lastname: Kettunen
authors.forename: Carita
authors.initials: C
authors.lastname: Eklund
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Hannu
authors.initials: H
authors.lastname: Päivä
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004548:Elasticity; D005260:Female; D005387:Finland; D056726:Genetic Association Studies; D006239:Haplotypes; D006306:Health Surveys; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein