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Association of common CRP gene variants with CRP levels and cardiovascular events

D T Miller1, R Y L Zee, J Suk Danik

  • 1Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

Annals of Human Genetics
|November 4, 2005
PubMed

Insights

Genetic variations in C-reactive protein (CRP) influence its levels, a key marker for cardiovascular disease risk. Some CRP gene variants are linked to higher or lower CRP levels, but not directly to heart attack or stroke risk.

Area of Science:

  • Genetics
  • Cardiovascular Disease
  • Biomarkers

Background:

  • C-reactive protein (CRP) is a recognized indicator of atherosclerotic cardiovascular disease (ASCVD) risk.
  • Understanding genetic contributions to CRP levels is crucial for risk assessment.

Purpose of the Study:

  • To identify common single nucleotide polymorphism (SNP) variants within the CRP gene.
  • To investigate the association of these SNPs with baseline CRP levels in multiple healthy cohorts.
  • To determine if CRP-associated SNPs correlate with the risk of myocardial infarction (MI) or ischemic stroke.

Main Methods:

  • Resequencing of the CRP gene to identify common SNP variants.
  • Association studies in three independent cohorts: Women's Health Study (WHS), Pravastatin Inflammation/CRP Evaluation (PRINCE), and Physicians' Health Study (PHS).
  • Prospective, nested case-control study within the PHS cohort to assess incident cardiovascular events.

Main Results:

  • Four SNPs were consistently associated with higher CRP levels, and two with lower CRP levels across all cohorts (p < 0.05).
  • Functional roles suggested for the 5'-flanking SNP -286C>T>A and the 3'-UTR SNP 1846G>A.
  • No identified CRP-level-associated SNPs predicted risk of MI or ischemic stroke.
  • One SNP, -717A>G, unrelated to CRP levels, showed association with decreased MI risk (p = 0.001).

Conclusions:

  • Genetic variations significantly influence CRP levels, a predictor of atherothrombotic events.
  • The relationship between CRP levels and cardiovascular risk involves complex interactions between genetic and environmental factors.
  • Specific CRP SNPs may not directly mediate cardiovascular risk despite their effect on CRP levels.

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