Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events.

Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 29.98). 01/2007; 296(22):2703-11. DOI: 10.1001/jama.296.22.2703
Source: PubMed

ABSTRACT C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD).
To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events.
In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003).
Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up.
In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality.
Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionSingle nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to pro-inflammatory stimuli. Previous reports suggest these effects may have an impact on clinical decision-making based on CRP, for example DAS28. We aimed to investigate the possible association between 7 CRP SNPs, their haplotypes, and the serum level of CRP as well as the DAS28 score in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.Methods Overall, 315 disease-modifying anti-rheumatic drugs and steroid naïve RA patients with disease duration <6 months were included from two randomized controlled trials (the CIMESTRA and OPERA trials). Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations to CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.ResultsThe minor allele of rs1205 C¿>¿T was associated with decreased CRP levels at baseline (P =0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P =0.005) compared to homozygosity of the major allele, but no association was observed at year one (P =0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P =0.043), although no effect was observed at year one (P =0.466). No other SNP or haplotype was associated with CRP at baseline or year one (P ¿0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or year one (P ¿0.10).Conclusion CRP genotype and haplotype were only marginally associated with serum CRP levels and without any association to the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.Trial registrationThe OPERA study is registered at (NCT00660647). The Cimestra study is not listed in a clinical trials registry due to inclusion of patients between October 1999 and October 2002.
    Arthritis Research & Therapy 10/2014; 16(5):475. · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Low handgrip strength is one component of frailty, characterized by loss of reserves, including energy, physical ability, cognition and health. This study rated effect of five single-nucleotide polymorphisms (SNPs) in C-reactive protein (CRP) gene on the serum CRP level and handgrip strength in elderly Taiwanese. Five SNPs (rs2794520, rs1205, rs1130864, rs1800947, and rs3093059) of CRP gene were utilized to genotype 472 unrelated elderly subjects (mean age 73.8years). Handgrip strength was measured by handgrip dynamometer (TTM Dynamometer, Tsutsumi, Tokyo). Our study demonstrated minor alleles of rs2794520 and rs1205 were C, whereas they were T in most ethnic groups. There exist significant associations of three CRP polymorphisms (rs2794520, rs1205 and rs3093059) with serum CRP level and handgrip strength. All three had simultaneous influence on raising CRP levels and reducing handgrip strength. Genotype and sex interactions emerged for rs2794520 and rs1205 in relation to CRP levels (P<0.05). In addition, haplotype C-C-C-C-C was associated with higher levels of CRP (exp(β)=1.45; P<0.001) and lower handgrip strength (β=-1.00kg, P<0.05). We conclude SNPs rs2794520, rs1205, and rs3093059 of CRP gene, as well as haplotype C-C-C-C-C may be important biomarkers for susceptibility to low handgrip strength and high serum CRP level in elders; further studies are required.
    Experimental Gerontology 05/2014; · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the association between four polymorphisms in the CRP gene with serum C-reactive protein (CRP) levels, prevalence and severity of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients.
    BioImpacts : BI. 09/2014; 4(3):133-9.

Full-text (2 Sources)

Available from
Jun 2, 2014