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

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.