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Genetic Origins of Heart Disease Uncovered

by Kathy Jones on August 5, 2010 at 9:22 PM
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 Genetic Origins of Heart Disease Uncovered

Scientists are reporting that a massive genome sweep of 100,000 people has uncovered dozens of gene variants that can boost two types of blood lipids, or fat, known to contribute to heart disease

Taken together, the 95 variants -- 59 spotted for the first time -- account for up to a third of genetically-determined cholesterol and triglyceride levels.


The findings, published as two studies in Nature, open up multiple paths for the design of drugs that could help tame "bad" cholesterol and its associated diseases, the researchers said.

So-called LDL cholesterol delivers essential fatty acids from the liver to other tissues, and triglycerides provide a key source of energy.

In excess, however, they can lead to strokes, artery disease and heart attacks.

Cardiovascular disease is especially prevalent in rich nations and the leading cause of death worldwide.

Smoking, rich food, lack of exercise, alcohol abuse and other lifestyle habits can all push up blood levels of these harmful fats -- and the cardiovascular troubles that come with them.

But genetic makeup can play an important role too, and the new research provides the most precise pictures to date of exactly which genes are in play.

In the core study, a consortium of 200-odd scientists led by Massachusetts General Hospital's Sekar Kathiresan scanned the DNA of more than 100,000 people of European origin for "genetic hotspots" linked to altered levels of blood fats.

The large sampling size made it possible to find suspect locations on the genome that had gone unnoticed in earlier sweeps.

It also shed light on the cellular and molecular mechanisms by which these genetic variants contribute to health failures, the researcher said.

"The new findings point us to specific genetic signposts that allow us to understand more fully why many people from all walks of life have abnormal levels of cholesterol and other blood lipids that lead to heart disease," said co-author Christopher O'Donnell, associate director of the Framingham Heart Study in Massachusetts.

The scientists took the results a step further by validating the link between three specific gene variants and lipids in experiments on genetically altered mice.

They showed that the results also pertain to people of different ethnic origins, including African, East Asian and South Asian.

In the second study -- focused on a single gene variant -- a team co-led by Daniel Rader at the University of Pennsylvania was able to bridge the gap between a DNA snippit and the disorder it is suspected of provoking.

By designing lab mice that either produced too much or not enough of a protein called sortilin, they were able to show that its coding gene, Sort1, can dramatically alter cholesterol in the blood.

"One of the criticisms of genome-wide association studies (GWAS) has been that they fail to identify specific genes that cause disease," Rader said.

"These results identify Sort1 as the causal gene responsible for the association of a part of chromosome 1 with cholesterol levels in the blood and therefore heart disease," he said in statement.

Major funding for the multi-year study came from several branches of the US National Institutes of Health.

Source: AFP

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