Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis
Introduction
Elevated C-reactive protein (CRP) concentrations are associated with increased risk of future myocardial infarction (MI) and stroke among apparently healthy men and women [1], [2], [3], as well as those with stable angina pectoris [4] or acute coronary ischemia [5]. As CRP is a critical component of the innate immune response, it is likely that CRP also has major genetic determinants.
We, therefore, sought to (a) determine the population frequency of a recently described 1059G/C polymorphism within exon 2 of the CRP gene in a large prospective cohort [6]; (b) determine whether this polymorphism relates to plasma concentrations of CRP; and (c) evaluate whether this polymorphism is associated with an altered risk of developing arterial thrombosis.
Section snippets
Methods
We employed a nested, case control study design in a prospective cohort of 14 916 initially healthy American men [1]. For this analysis, cases were those initially healthy study participants who subsequently developed a first arterial thrombosis (nonfatal MI, nonfatal stroke, or cardiovascular death) during a mean follow-up of 8.6 years. For each case, a control was selected at random from those study participants who remained free of reported cardiovascular disease and who met the matching
Results
Table 1 presents baseline characteristics of the study population. As expected, apparently healthy men who went on to suffer a first ever MI, stroke, or cardiovascular death (cases) were more likely than their matched controls at baseline to be overweight, hypertensive, or hyperlipidemic. Baseline CRP concentrations were significantly higher among cases than controls (P=0.006), consistent with previous findings [1]. Overall, 1280 study participants (88.2%) were found to carry the GG genotype,
Discussion
The current data suggest that both inherited and acquired determinants of plasma CRP concentrations exist and thus that each of these factors will need careful evaluation in order to understand the complex role inflammation plays in athero-thrombosis. Prior work from population studies indicate that obesity, age, smoking, diet, chronic infection, extent of sub-clinical atherosclerosis, and medications such as hormone replacement therapy and statins are all involved in the expression of CRP
Acknowledgments
This study was supported by the National Heart Lung and Blood Institute (HL58755, HL63293), the American Heart Association, and the Doris Duke Charitable Foundation.
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