Elsevier

Atherosclerosis

Volume 162, Issue 1, May 2002, Pages 217-219
Atherosclerosis

Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis

https://doi.org/10.1016/S0021-9150(01)00703-1Get rights and content

Abstract

While increased concentrations of C-reactive protein (CRP) are associated with increased vascular risk, little information is available describing genetic determinants of this effect. In a large prospective cohort of apparently healthy men, we found plasma CRP concentrations to be significantly reduced among carriers of a 1059G/C polymorphism in the human CRP gene (GC or CC) as compared with non-carriers (GG). However, the polymorphism examined was not significantly associated with risk of arterial thrombosis despite the fact that CRP concentrations are a potent independent predictor of future vascular events in this cohort. These data suggest that genetic and environmental determinants each importantly contribute to the vascular risk associated with inflammation.

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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