Search for cholesterol absorption genes narrows to two chromosome regions

Two people eat the same egg, cheese and ham muffin for breakfast, yet one absorbs significantly more cholesterol into his or her blood than the other. Why?

The answer, and all of its implications for combating heart disease, remains stubbornly hidden within our DNA. In recent genetic studies with lab mice, however, researchers at The Rockefeller University have begun to close in on the culprit genes.

"By determining the genetic basis behind the observation that some people absorb 25 percent of cholesterol from their diet, while others absorb up to 75 percent, we hope to develop new treatments to protect this latter group," says senior co-author Jan. L. Breslow, M.D., head of The Rockefeller University's Laboratory of Biochemical Genetics and Metabolism and former national president of the American Heart Association.

The researchers hope that the identification of genes that regulate cholesterol absorption in mice will lead them to the location of similar genes in humans - and ultimately to the development of drugs that specifically reduce cholesterol absorption and protect against coronary heart disease, the number one cause of death in the United States.

In the Dec. 10 issue of the Proceedings of the National Academy of Sciences (published online Nov. 22), the Rockefeller scientists report the use of mouse "genetic linkage mapping" technology to narrow the location of genes responsible for regulating the absorption of plant fatty molecules called "plant sterols" - markers of cholesterol absorption - to two distinct regions on chromosome 2 and 14.

While the exact location of the genes has not been deduced, the results indicate that the researchers have indeed uncovered their general vicinity: one of the putative sites has an incredibly high probability - a billion to one - of carrying the suspected genes.

"We are excited because our data analysis shows that cholesterol absorption genes are very likely hiding in chr

Contact: Whitney Clavin
Rockefeller University

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