Common gene raises heart risk, studies find

[Al-khiyal]

NEW YORK, May 3, 2007 -- Two rival teams of scientists have discovered a genetic variation that increases the risk of heart disease, the leading cause of death worldwide, by up to 60 percent in people of European descent. They hope that a test for the variant will enable physicians to assess patients at risk more accurately and to recommend early intervention.

The variant is so common that about 50 percent of people in European populations carry one copy of it, and about 20 percent of people have inherited two copies, one from each parent. Carriers of a single copy have a 15 to 20 percent greater risk of heart disease, while carriers of two copies are up to 60 percent more likely to develop heart disease than people who have none.

The risk is even higher for people who suffer heart disease at an early age, defined as men under 50 and women under 60.

The finding, being published Friday in the journal Science, is one of a spate of discoveries about the genetic basis of common diseases. Last week seven new genetic variants involved in the most common form of diabetes were identified, and a batch of new genes from other common diseases is expected to be reported in the next few weeks.

These discoveries are the long-promised fruit of the $3 billion Human Genome Project, which was essentially completed in 2003. There have been two principal approaches to scanning the genome for disease genes, which are culminating in photo-finish results by the proponents of each method.

One competitor is Decode Genetics, a private company based in Reykjavik, that has used the comprehensive health care records and known genealogy of the Icelandic population to track disease. Decode has dominated the gene-finding field for the past several years.

Decode's rivals are medical researchers based at universities in the United States and Europe. They have made a slower start because, without an Icelandic-type data set, they have had to wait for construction of the Hap Map, a survey of common genetic variations on the human genome in Africans, Asians and Europeans. These common variations, known as SNPs or "snips," are thought to be the genetic basis of the common diseases.

Both sides have been greatly helped by a technical development, the construction by companies like Affymetrix and Illumina of instruments known as microarrays or chips that can now detect up to 500,000 snips. With the chips, the genomes of patients with a disease can be compared with those of healthy people, allowing snips that seem associated with the disease to be identified.

Last week both Decode and three academic consortia reported new diabetes genes. The reports this week on heart disease come from Decode and another academic consortium, led by Ruth McPherson of the University of Ottawa Heart Institute and Jonathan Cohen of the University of Texas Southwestern Medical Center in Dallas.

McPherson said that it came as a "complete surprise" that Decode had submitted its report at the same time to the same journal, but that "at the end of the day we are very happy they came out with the same result." Both groups identified snips in a small region of Chromosome 9 (the human genome is packaged into 23 pairs) as being associated with higher risk of heart disease.

But as if to prove how much remains to be understood about human biology, the snips lie in a stretch of DNA that contains no gene or genetic element with known functional purpose. It is only on the basis of rigorous statistics that the two groups believe their snips must be causally associated with heart disease.

This means that the researchers still have no idea of the mechanism by which the snips raise the risk of heart disease. When the mechanism comes to light, it may be possible to design drugs that interfere with it so as to avert the risk.

Decode says it will use this and other heart-disease-related variants it has found as the basis for a test that gauges the inherited risk. But, McPherson said, "it would be unfortunate if snips using these tests were patented and physicians couldn't use them without paying a royalty to Decode.

A test would help address the big unanswered question in heart disease: for whom should the many available interventions be recommended? McPherson said. Risk is now assessed on conventional factors like smoking, but if a patient turned out to have two copies of the genetic variant, his risk would much higher than his physician may have estimated.

The new heart disease risk snip is much less common in Africans and African-Americans and seems not to be correlated with heart disease in these populations, the Ottawa-Dallas team reported.

The idea behind the Hap Map, that common genetic variants are associated with common diseases, assumes that natural selection is unable to get rid of disease genes that act only late in life, well after the age of reproduction. But the heart disease risk variant is so extraordinarily common that it may confer some unknown benefit.

Common gene raises heart risk, studies find

[Al-khiyal]

Scientists have discovered a strand of DNA that dramatically raises the risk of coronary heart disease and doubles the chances of younger people suffering a heart attack prematurely. The high-risk stretch of genes is common among Caucasian populations, with up to a quarter carrying copies that boost the risk of heart disease by 40% and increase the lifetime risk of a heart attack by 60%.

Early-onset heart attacks, occurring in men under 50 and women under 60, were found to be twice as likely among those who inherited the high-risk gene sequence from both their mother and father.

The strand of DNA, reported in the prestigious US journal Science today, is believed to be the most important genetic factor for heart disease yet found.

Two groups of researchers, working independently of each other, identified the gene sequence after comparing the entire genomes of more than 40,000 people. Researchers from one of the teams, a Reykjavik-based biotech company called deCODE, hopes to have a test for the gene variant available by the end of the year, to identify people most at risk of developing heart disease later in life. Those who test positive would be encouraged to reduce their risk of heart attack by taking cholesterol-lowering drugs such as statins, and encouraged to have heart scans to look for early signs of arterial disease.

The other team was led by Ruth McPherson at the University of Ottawa Heart Institute in Canada.

The twin studies reveal the dramatic influence that genetic factors have on the risk of heart disease, in addition to the well-documented effects of smoking, diet and exercise.

"This is likely to be the biggest genetic factor for heart disease and it gives a very dramatic increase in heart disease," said Kari Stefansson of deCODE. "Early-onset heart attacks unexpectedly take the lives of young people, and these are the heart attacks that are most important to prevent. If we can identify the risk factors, we have ways of dealing with the problem."

The strand of genes raises the risk of cancer by causing cells to multiply rapidly, causing a build up of cells in heart blood vessels and eventually causing them to become blocked.

Nilesh Samani, professor of cardiology at Leicester University, said the findings would help greatly to underestand heart disease, but a person's familial history of heart disease was still the best predictor of their risk. "It's a bit early to say a test is useful," he said.

DNA find may identify early heart risk victims