Worldwide, coronary heart disease (CHD) is the leading cause of death. According to a study published online in The Lancet, anti-inflammatory medications may become a new way to prevent and treat the disease.
Using a gene analysis tool called the Cardiochip, the researchers examined a specific gene variant associated with inflammation and heart disease. The chip was designed by Brendan J. Keating, Ph.D., co-author of the study and a researcher in the Center for Applied Genomics at The Children's Hospital of Philadelphia.
Even though researchers are aware of the association between inflammation and atherosclerosis - a disorder in which fat, cholesterol, and other fatty deposits build up in the walls of arteries - they have been unable to find an inflammatory agent that causes the diseases, until now. In addition, researchers did not know whether a drug targeted at reducing inflammation might treat the disease.
The team focused on the signaling protein interleukin-6 receptor (IL6R). IL6R is found in the blood and increases inflammatory responses.
"This study provides robust evidence that IL6R is implicated in coronary heart disease. Furthermore, our analysis showed that an existing anti-inflammatory drug, acting on this receptor, may offer a new potential approach for preventing CHD."
The meta-analysis study was conducted by the IL6R Mendelian Randomization Analysis Consortium, and international team of investigators led by Dr. Juan Pablo Casas, Professor Aroon. D. Hingorani, and Dr. Daniel I. Swerdlow, all of University College London, UK.
The researchers examined data from 40 previous studies that involved almost 133,500 individuals from Europe and the United States. Mendelian randomization is a research technique that utilizes knowledge of genes and biological mechanisms in order to figure out the likely effects of a new medication before a clinical trial is conducted, with its potential risk of adverse effects and high cost.
In the same issue of The Lancet, an associated report conducted by the IL6R Genetics Consortium and Emerging Risk Factors Collaboration, discovered that a genetic variant of the IL6R gene, which carries the code for the IL6R protein, decreases inflammation and therefore reduces the risk of heart disease.
The primary focus of the study Keating participated in was on SNPs (single nucleotide polymorphisms) single-base changes in the IL6R gene that codes for the IL6R protein.
The researchers used the IBC Human CVD BeadChip (a DNA array), also called the Cardiochip. The chip, which contains DNA markers for 2,000 gene variants implicated in cardiovascular disease, was developed in 2006 by Keating and has been used in several large gene studies.
When the chip is brought into contact with test samples of DNA from study participants, it identifies specific SNPs in the sample - gene variants that could potentially affect biological functions as well as risks of cardiovascular disease among the study participants.
The researchers discovered that one SNP, the gene variant rs8192284, changed numerous biological markers linked to inflammation. These results were comparable to results found in studies of tocilizumab, an anti-inflammatory drug currently used to treat individuals suffering with rheumatoid arthritis. This medication decreased the painful inflammation common in rheumatoid arthritis by preventing the action of IL6R.
After examining data from patients with CHD and controls, the researchers also found that individuals carrying the gene variant had a lower risk of developing CHD.
"What this tells us is that IL6R blockers such as tocilizumab mimic the benefits of having this gene variant. A next step will be for cardiology researchers to design and carry out clinical trials to determine whether tocilizumab or similar anti-inflammatory drugs will prevent heart disease."
Written by Grace Rattue