Large Gene Study Links Plaque In Heart Disease To Inflammation

Large Gene Study Links Plaque In Heart Disease To Inflammation03 Dec 2012-nbsp;-nbsp;-nbsp;


By linking 15 new genetic regions to coronary artery disease, a large international study sheds new light on the underlying causes of this most

common form of heart disease, which results from the build up of fatty material or plaque on the insides of the blood vessels of the heart. One finding suggests

some people may be genetically predisposed to the disease because they have inherited gene variants related to inflammation.

A report on the study was published in the journal Nature Genetics on 2 December.

Coronary artery disease is the the leading cause of death worldwide. The plaque build up in the walls of heart vessels, a process known as coronary

atherosclerosis, eventually makes them so narrow that it slows or stops the flow of essential blood and oxygen to the heart, causing chest pain and potentially

lethal heart attacks.

Massive Meta-Analysis

A consortium of more than 170 researchers worked on the study, a massive meta-analysis that pooled genetic data from over 190,000 research participants to provide insights into the molecular pathways causing the plaque build up seen in coronary artery disease.

The 15 new genetic regions brings to 46 the total number of genetic links with heart disease found through genome-wide association studies (GWAS).

The researchers found that 25% of the genetic regions were also strongly linked with cholesterol, especially with high levels of of LDL, the so-called "bad

cholesterol". And a further 10% of the genetic regions were linked to high blood pressure.

Both these conditions are known risk factors for coronary artery disease.

Inflammation: Cause or Effect?

One of the study's lead authors, Themistocles (Tim) Assimes, an assistant professor of medicine at Stanford in the US, suggests in a press statement:

"Perhaps the most interesting results of this study show that some people may be born with a predisposition to the development of coronary atherosclerosis

because they have inherited mutations in some key genes related to inflammation."

"There has been much debate as to whether inflammation seen in plaque build up in heart vessels is a cause or a consequence of the plaques themselves," says

Assimes, who nonetheless suggests:

"Our network analysis of the top approximately 240 genetic signals in this study seems to provide evidence that genetic defects in some pathways related to

inflammation are a cause."


Assimes says the signals that do not point to already known risk factors may be revealing new mechanisms of disease.

He urges there is now a need to work quickly to better understand how these genetic regions are linked to heart disease, and thus help to develop new drugs to

prevent it.


Subtle and Combined Effects Require Huge International Effort to Discover Genetic Causes of Disease

Researchers started using GWAS in 2005 as a way to quickly scan entire genomes and find genetic variants that predispose people to disease. A genetic variant,

or "polymorphism", is a piece of DNA that varies from person to person, like different spellings of the same word or phrase.

However, as revealed by this and other huge international efforts, such a study last year that found 17 new genetic variants tied to an increased risk of coronary artery disease, what is

emerging is that conditions like heart disease involve the combined and subtle effects of far more genetic variants than initially expected.

To analyze these subtle and combined effects effectively, researchers have to carry out huge studies that pool data from a large number of participants. This

calls for greater collaboration, in well-coordinated worldwide consortia, if all the genetic causes of heart disease are to be found.


Written by Catharine Paddock PhD








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