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: 35.29). 01/2007; 296(22):2703-11. DOI: 10.1001/jama.296.22.2703
Source: PubMed


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.

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    • "It has been shown that elevated serum CRP is a risk factor for CHD, and there is a relationship between increased serum levels of CRP with various CHD risk factors, particularly diabetes and hypertension [22, 23]. On the other hand, it has been reported that several polymorphisms in the CRP gene are associated with variation in the concentration of this protein, which is increased with the TT and GG genotypes of the SNPs rs30864 and rs2794521, respectively, and decreased with the AA genotype of rs1205. "
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    ABSTRACT: Objective: We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease. Methods: We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. Results: The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P < 0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. Conclusions: The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.
    Experimental Diabetes Research 09/2012; 2012(3):982683. DOI:10.1155/2012/982683 · 4.33 Impact Factor
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    • "The concentration of CRP may be an indicator of endothelial dysfunction as well as a mediator of insulin resistance and arterial injury (Sanchez-Recalde and Carlos, 2001). Several studies have reported that variants in the CRP gene are associated with variations in blood levels of CRP in cardiovascular and other diseases such as diabetes, microangiopathic stroke, metabolic syndrome, and hypertension (Brull et al., 2003; Chen et al., 2005; Szalai et al., 2005; Lange et al., 2006; Komurcu-Bayrak et al., 2009; Hsu et al., 2010; Kuhlenbaeumer et al., 2010). "
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    ABSTRACT: Variants in the C-reactive protein (CRP) gene have been found to be associated with various phenotypic traits. We evaluated the effect of four SNPs in the CRP gene on serum levels of protein and body mass index (BMI) in 150 unrelated Mexican subjects from 18 to 25 years old, without hypertension, non-overweight, and without inflammatory diseases, non-smoking and non-consumers of alcohol. Subjects were measured for BMI, waist circumference, blood pressure, and serum glucose and triglycerides. The identification of SNPs was performed by PCR-RFLP. Three of the four SNPs were associated with variation in serum levels of CRP, increased in TT (rs1130864) and GG (rs2794521) genotypes, and decreased in the AA genotype of rs1205. The TT genotype was associated with a significant increase in BMI (β = 1.1 kg/m², P = 0.04). Two haplotypes were significantly associated with increased serum levels of CRP, but not with BMI. We conclude that variation in the CRP gene affects serum protein levels.
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    • "The haplotype frequencies were generated using SNPHAP (Clayton, 2002; version 1.3; available online at with an estimation-maximization algorithm. Six SNPs (i.e., rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) were used to generate five common haplotypes that determine about 10% of the interindividual variability in CRP levels in the absence of infection [27, 31]. Haplotypes with prevalence larger than 3% were selected for further comparison and named haplotype 1, haplotype 2, haplotype 3, haplotype 4, and haplotype 5. "
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