Findings no causal relationship to C-reactive protein with CHD

An analysis of the association between genetic variation, biomarkers of inflammation C-reactive protein (CRP), with cardiovascular disease is not a causal relationship, according to a study of the 1st edition July JAMA.

Coronary heart disease (CHD) is the leading cause of death in the world. Inflammation plays an important role in the development of CHD, at each stage of the initiation of the progression and plaque rupture. CRP is currently the most commonly used biomarkers of inflammation in the background information in the article. "There is great interest to determine whether CRP has a causal role in coronary artery disease or if only one brand of CRP to atherosclerosis underlying," write the authors.

Paul Elliott, FRCP, of Imperial College London and his colleagues, a genetic study of the association, common genetic loci (the page of a gene on the chromosome), the CRP and uses the concept of Mendelian randomisation (random allocation of alleles - another form of a gene in one place - the design) to verify the possible causal relationship with levels of CRP heart. First, a genome association (n = 17,967) and replication of the study (n = 13,615) were produced for genetic loci under the CRP plasma concentrations. Data collection took place between 1989 and 2008 and genotyped between 2003 and 2008. The researchers conducted a study of Mendelian randomization closely Single-nucleotide polymorphism (SNP) in the CRP locus and publishes data on other variants of CRP, a total of 100,823 cases and 28,112 controls, for the union of the CRP variants with heart disease. These results were compared with the results of the meta-analysis of observational studies of CRP and the risk of cardiovascular disease.

The researchers found: "The present genome-wide association study confirms the association of common genetic variants in leprosy, IL6R, CRP, and HNF1a loci and ApoE-CI-CII cluster-CRP levels. However, the most small allele of SNP rs7553007 and other variants in the CRP-Locus Mendelian randomization in our study is not related to cardiac risk. "

The authors write that the alternatives that Mendelian randomization in this study are related to approximately 20% lower CRP levels, a reduction of 6 per cent of cardiac risk provided by the meta-analysis of studies monitoring the risk of coronary heart disease . "The lack of cooperation with KHK of genetic variants in the CRP-Locus suggested that the coupling of observational data of CRP and coronary heart disease may be rebutted [factors affecting the results] CHD connection with other risk factors, or a secondary inflammatory reaction in the context of atherosclerosis (reverse causality), rather than a causal relationship. "

"In short, it is clear that our Mendelian randomization study of more than 28,000 cases and 100,000 controls no association of variants in the CRP-Locus and coronary heart disease, arguing against a causal role in atherosclerosis CRP. In addition This study suggests that the development of targeted therapeutic strategies for reducing the plasma levels of CRP is unlikely fertile, researchers.