The study involved analyzing various lipids, or fats, in blood and bile to find differences in cholesterol metabolites, sequencing candidate genes of interest to find mutations, and determining the impact of each mutation by genetic analyses. This led to the discovery that the ABCB4 gene, which encodes a protein known to transport fats from the liver into bile to facilitate excretion of cholesterol from the body, is defective in the high responders. Malfunction of the ABCB4 protein was found to impair cholesterol excretion, causing bad cholesterol to accumulate in the blood when a high-cholesterol diet is consumed.

"This is the first report to show that ABCB4 has a role in controlling blood cholesterol levels in response to dietary cholesterol in an animal model," said VandeBerg.

The next step is to determine if any ABCB4 mutations have an effect on levels of LDL cholesterol in humans who consume a high cholesterol diet. "If we can identify early in life those people who are going to be adversely affected by consumption of high levels of cholesterol, we can encourage their parents and them to receive individually tailored counseling to establish dietary habits that protect them from cardiovascular disease," VandeBerg said.

Source: Southwest Foundation for Biomedical Research