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Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey.
Circulation. 2006 Dec 05; 114(23):2458-65.Circ

Abstract

BACKGROUND

Increased serum C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. Previous studies have suggested that genetic variation within the CRP gene is associated with serum CRP.

METHODS AND RESULTS

We genotyped CRP genetic variants in 7159 individuals from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is American population-based sample linked to hundreds of phenotypes, including CRP; however, the CRP assay used in this survey is not a high-sensitivity CRP assay, and 65% of participants (n=4679) had CRP measurements at or below the level of detection. Despite these limitations, we identified specific CRP single-nucleotide polymorphisms (SNPs) and haplotypes associated with serum CRP levels in the general population. Two variants were associated with increased levels of serum CRP: SNP rs3093058 (in linkage disequilibrium with a CRP promoter SNP rs3093062) in the non-Hispanic black sample and the triallelic promoter SNP rs3091244 in the non-Hispanic black and Mexican American samples. Two other SNPs were associated with decreased levels of serum CRP in either the non-Hispanic black (rs1205 and rs2808630) or Mexican American (rs1205) samples. Three haplotypes inferred from 7 SNPs (ATTGCGA, TTAGCGA, and AAAGAGA) were associated (P < or = 0.01) with increased levels of serum CRP in the non-Hispanic black sample; 2 haplotypes (ATTGCGA and AAAGCGA) were associated (P < 0.05) with increased levels in the Mexican American sample; and 1 haplotype (AAAGCGA) was associated (P < 0.03) with increased levels in the non-Hispanic white sample. Post hoc analysis suggests that the AA genotype of the triallelic SNP rs3091244, after adjustment for covariates, was associated with prevalent coronary heart disease in the non-Hispanic white population sample.

CONCLUSIONS

Genetic variation within CRP is associated with serum CRP levels in the general population and may be associated with prevalent coronary heart disease.

Authors+Show Affiliations

Department of Genome Sciences, University of Washington, Seattle, USA. crawford@chgr.mc.vanderbilt.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17101857

Citation

Crawford, Dana C., et al. "Genetic Variation Is Associated With C-reactive Protein Levels in the Third National Health and Nutrition Examination Survey." Circulation, vol. 114, no. 23, 2006, pp. 2458-65.
Crawford DC, Sanders CL, Qin X, et al. Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey. Circulation. 2006;114(23):2458-65.
Crawford, D. C., Sanders, C. L., Qin, X., Smith, J. D., Shephard, C., Wong, M., Witrak, L., Rieder, M. J., & Nickerson, D. A. (2006). Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey. Circulation, 114(23), 2458-65.
Crawford DC, et al. Genetic Variation Is Associated With C-reactive Protein Levels in the Third National Health and Nutrition Examination Survey. Circulation. 2006 Dec 5;114(23):2458-65. PubMed PMID: 17101857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey. AU - Crawford,Dana C, AU - Sanders,Christopher L, AU - Qin,Xiaoting, AU - Smith,Joshua D, AU - Shephard,Cynthia, AU - Wong,Michelle, AU - Witrak,Laura, AU - Rieder,Mark J, AU - Nickerson,Deborah A, Y1 - 2006/11/13/ PY - 2006/11/15/pubmed PY - 2006/12/30/medline PY - 2006/11/15/entrez SP - 2458 EP - 65 JF - Circulation JO - Circulation VL - 114 IS - 23 N2 - BACKGROUND: Increased serum C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. Previous studies have suggested that genetic variation within the CRP gene is associated with serum CRP. METHODS AND RESULTS: We genotyped CRP genetic variants in 7159 individuals from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is American population-based sample linked to hundreds of phenotypes, including CRP; however, the CRP assay used in this survey is not a high-sensitivity CRP assay, and 65% of participants (n=4679) had CRP measurements at or below the level of detection. Despite these limitations, we identified specific CRP single-nucleotide polymorphisms (SNPs) and haplotypes associated with serum CRP levels in the general population. Two variants were associated with increased levels of serum CRP: SNP rs3093058 (in linkage disequilibrium with a CRP promoter SNP rs3093062) in the non-Hispanic black sample and the triallelic promoter SNP rs3091244 in the non-Hispanic black and Mexican American samples. Two other SNPs were associated with decreased levels of serum CRP in either the non-Hispanic black (rs1205 and rs2808630) or Mexican American (rs1205) samples. Three haplotypes inferred from 7 SNPs (ATTGCGA, TTAGCGA, and AAAGAGA) were associated (P < or = 0.01) with increased levels of serum CRP in the non-Hispanic black sample; 2 haplotypes (ATTGCGA and AAAGCGA) were associated (P < 0.05) with increased levels in the Mexican American sample; and 1 haplotype (AAAGCGA) was associated (P < 0.03) with increased levels in the non-Hispanic white sample. Post hoc analysis suggests that the AA genotype of the triallelic SNP rs3091244, after adjustment for covariates, was associated with prevalent coronary heart disease in the non-Hispanic white population sample. CONCLUSIONS: Genetic variation within CRP is associated with serum CRP levels in the general population and may be associated with prevalent coronary heart disease. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/17101857/Genetic_variation_is_associated_with_C_reactive_protein_levels_in_the_Third_National_Health_and_Nutrition_Examination_Survey_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.106.615740?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -