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Seven New Cholesterol Genes Discovered

SUNDAY Jan. 13, 2008 -- Seven new cholesterol-regulating genes, some of which influence the risk of heart disease, have been identified in an international study of almost 20,000 people in three countries.

"I would predict that some of these genes will be the targets for future drugs," said the study's senior author, Goncalo Abecasis, an associate professor of biostatistics at the University of Michigan School of Public Health.

In their report, published in the Jan. 13 issue of Nature Genetics., the researchers also confirmed the role of 11 previously identified cholesterol-related genes in the risk of heart disease.

"What was most exciting was that only the genetic changes that affect LDL cholesterol influence the risk of heart disease," Abecasis said. "Every genetic change that raises the level of LDL cholesterol influences the risk of heart disease."

LDL cholesterol is well known to be the "bad" kind that forms plaques that eventually can block arteries, causing heart attacks and other cardiovascular troubles. LDL cholesterol is the target of statins, drugs given to reduce coronary risk. HDL cholesterol is the "good" kind, which does not contribute to plaque formation.

"The conventional wisdom is that HDL cholesterol is good for you," Abecasis said. "But in our studies we found no major impact from those genes changing HDL cholesterol levels."

The research, done in collaboration with University of North Carolina and Harvard University researchers, started with genetic studies of 8,800 people from Italy, Sweden and Finland.

The researchers examined more than 2 million genetic variations in those individuals, eventually concentrating on 25 genetic variants, which together are responsible for about 25 percent of levels of blood lipids such as cholesterol.

The study associated incidence of different variants with the incidence of heart disease in those individuals. The results were then confirmed in a study of 11,000 individuals from the three populations.

Future research centering on the newly identified genes could produce "drugs that are as effective as statins in affecting the risk of heart disease," Abecasis said.

Another paper in the same issue of the journal reported the possible discovery of the long-sought "thrifty gene," whose existence was proposed more than three decades ago.

A study of more than a half-million genetic variants in 2,000 Europeans and Indian Asians found that a gene designated MLXIPL works the way the thrifty gene is said to do, turning excess blood glucose into fat tissue.

"These genes are advantageous during times of famine," said research leader Dr. James Scott, a professor of cardiovascular medicine at Imperial College in London.

However, in this era of plenty, the thrifty gene can be a serious problem.

"It's hard to say we've proved that it is a thrifty gene," Scott said. "But it looks like it has all the characteristics of such a gene. We hope this goes a long way toward proving it."

The thrifty gene would be "part of the very complex genetics of a complex disease such as obesity or of heart disease," Scott said. "This would be another step on the pathway of understanding why a person's family history is an indication of the risk of cardiovascular disease."

More information

The different cholesterols are described by the American Heart Association.

Posted: January 2008


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