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European Heart Journal Advance Access published online on May 3, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl018
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European Heart Journal © The European Society of Cardiology 2006; all rights reserved
Received November 30, 2005
Revised March 10, 2006
Accepted March 30, 2006

Clinical research

C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam Study

Isabella Kardys 1, Moniek P.M. de Maat 2, André G. Uitterlinden 3, Albert Hofman 1, and Jacqueline C.M. Witteman 1 *

1 Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands
2 Department of Hematology, Erasmus MC, Rotterdam, The Netherlands
3 Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

* To whom correspondence should be addressed.
Jacqueline C.M. Witteman, E-mail: j.witteman{at}erasmusmc.nl


  Abstract

Aims C-reactive protein is associated with risk of cardiovascular disease. However, whether C-reactive protein is a marker of severity of cardiovascular disease or actually is involved in its pathogenesis remains unknown. We investigated the relation between C-reactive protein haplotypes, representing the comprehensive variation of the C-reactive protein gene, and coronary heart disease.

Methods and results The Rotterdam Study is a prospective population-based study among men and women aged 55 years and older. C-reactive protein was associated with risk of coronary heart disease, with a multivariable adjusted hazard ratio of 1.9 (95% CI 1.5-2.4) for the highest vs. the lowest quartile. Four C-reactive protein haplotypes were present with overall frequencies of 32.8, 31.7, 29.5, and 5.9%. C-reactive protein serum levels were significantly different according to C-reactive protein haplotypes. C-reactive protein haplotypes were not associated with coronary heart disease.

Conclusion Steady-state C-reactive protein serum level is influenced by C-reactive protein gene haplotypes. Although elevated C-reactive protein level has lately been found to be a consistent and relatively strong risk factor for cardiovascular disease, our study does not support that the common variation in the C-reactive protein gene has a large effect on the occurrence of coronary heart disease.

Keywords: Coronary heart disease; Inflammation; C-reactive protein; Genetics; Epidemiology.
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