Many prospective studies have reported associations between circulating C-reactive protein (CRP) and risk of coronary heart disease (CHD), but the causal nature of any relationship remains uncertain. To help assess the likelihood of causality, studies of CHD are being conducted, involving measurement of common polymorphisms of the CRP gene known to influence its circulating concentrations, thereby utilising these variants as proxies for circulating CRP levels. By generating and subsequently analysing data from several studies examining the association between relevant CRP polymorphisms and risk of CHD, the CRP Coronary Disease Genetic Studies Collaboration (CCGC) will undertake a Mendelian randomisation analysis to help assess the likelihood of any causal relevance of CRP to CHD. A central database is being established containing individual data on CRP polymorphisms, circulating CRP levels, and major coronary outcomes as well as age, sex and other characteristics relevant to coronary risk. This collaboration comprises, at present, a total of about 40 000 CHD outcomes in approximately 175 000 participants from 42 studies. Such numbers will help to determine the likelihood and magnitude of any causal association between plasma CRP levels and subsequent CHD, advancing understanding of the relevance of low-grade inflammation to CHD and indicate whether or not CRP itself is involved in long-term pathogenesis.
The CCGC is jointly coordinated by the University of Cambridge, the London School of Hygiene and Tropical Medicine, University College London and McMaster University.
Funding: The coordinating centre is supported by grant SP/08/007 from the British Heart Foundation. A variety of sources have supported recruitment, follow-up and laboratory measurements in the contributing studies.