Analysis of proteins contained within the blood of people in population biobank studies has identified potential drug targets for the treatment of ischaemic heart disease (IHD). The study by researchers at Oxford Population Health and Peking University is published today in the Journal of the American College of Cardiology (JACC).
Proteins play a key role in health and disease and most drugs target proteins. Advances in techniques to study proteins now enable researchers to analyse several thousand proteins in very small quantities of blood samples. Analysing these proteins alongside genetic markers and comparing the results from people who have a disease with those who do not can uncover proteins that are linked to disease and the genetic variants that can influence the level of these proteins.
Additional analysis of the associations between genetic markers and proteins in blood samples from people with IHD can discover proteins that may be responsible for causing diseases such as IHD, leading to new treatments and improved risk prediction.
The study used data from participants in the China Kadoorie Biobank (CKB), a long-term collaborative study between Oxford Population Health and Peking University, which recruited 0.5 million healthy adults from 10 diverse areas in China during 2004 and 2008. In this study, researchers analysed levels of 1,463 proteins in stored blood samples from 1,976 people who developed IHD after they had enrolled into the study and 2,001 people who did not have IHD by the time their blood samples were analysed.
The researchers wanted to understand whether or not their findings could be applied to other populations outside China so they replicated the study with data from the UK Biobank and the CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics) consortia (CC4D).
- Overall, 361 proteins were significantly associated with a risk of IHD in CKB, including proteins that are already being investigated as potential targets for disease prevention such as NT-ProBNP and PCSK9;
- Of the 361 proteins, 212 of them could be matched to genetic traits in the CKB population and analysis of 198 genetic variants in CC4D data identified 13 proteins that could be responsible for causing IHD;
- Further analysis of data from European populations replicated associations for four proteins (FURIN, F2R, ASGR1, and MMP3) with IHD;
- The similarity in the associations in two populations and further detailed analyses of the likely functions of these proteins provides strong support for these proteins being potential novel treatment targets for IHD.
Study author, Dr Mohsen Mazidi, Genetic Epidemiologist at Oxford Population Health, said ‘By combining analyses of plasma proteomics and genetics data in diverse populations, we identified multiple novel drug targets for ischaemic heart disease.’
Professor Liming Li, a senior author and CKB China Principal Investigator from Peking University, said ‘Most drugs target proteins and large biobank studies such as CKB provide a unique opportunity for undertaking cutting-edge discovery research related to drug development.’
Professor Zhengming Chen, a senior author and CKB UK Principal Investigator said ‘The results highlight the importance of proteomics for the discovery of novel treatment targets for ischaemic heart disease and the value of extending these analyses with other protein panels and in other disease areas.’