Genetically Elevated C-Reactive Protein and Ischemic Vascular Disease

• Published in: The New England journal of medicine Vol. 359; no. 18; pp. 1897 - 1908
• Main Authors: Zacho, Jeppe, Tybjærg-Hansen, Anne, Jensen, Jan Skov, Grande, Peer, Sillesen, Henrik, Nordestgaard, Børge G
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 30.10.2008
• Subjects: Atherosclerosis - blood; Biological and medical sciences; Biomarkers - blood; Blood tests; C-Reactive Protein - analysis; C-Reactive Protein - genetics; Cardiovascular disease; Causality; Cerebrovascular Disorders - blood; Cerebrovascular Disorders - genetics; Cohort Studies; Cross-Sectional Studies; Female; General aspects; Genetic Predisposition to Disease; Genotype & phenotype; Humans; Male; Medical sciences; Myocardial Ischemia - blood; Myocardial Ischemia - genetics; Polymorphism, Genetic; Proteins; Risk Factors; Medicine; Vascular disease; Acute phase protein; Ischemia; Cardiovascular disease; Genetics; C reactive protein
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0707402

In a study of four cohorts of patients from Denmark, the subjects were typed for four single-nucleotide polymorphisms in the gene for C-reactive protein (CRP). The resulting genotypes were correlated with an increase in CRP levels of up to 64%, a result predicting significantly increased risks of ischemic heart disease and ischemic cerebrovascular disease. However, no such increase in risk was observed, a result suggesting that the known association between CRP levels and vascular risk is not causal. Four cohorts of patients were typed for four single-nucleotide polymorphisms in the gene for C-reactive protein (CRP). Although the resulting genotypes were correlated with an increase in CRP levels of up to 64%, no increase in risk of ischemic heart disease or ischemic cerebrovascular disease was observed, suggesting that the association between CRP levels and vascular risk is not causal. Elevated plasma levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. 1 – 5 However, whether CRP is simply a marker for ischemic vascular disease or whether elevated CRP levels actually contribute directly to causing such disorders is presently unknown. This question has clinical importance, since several drugs that specifically lower CRP levels are being developed, 6 with the ultimate aim of preventing ischemic vascular disease. The random assortment of genes that occurs during gamete formation provides a relatively unbiased method of assessing whether risk factors that have a genetic component are in fact . . .