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article imageStudy Finds Surprises About Good, Bad Cholesterol

By Bob Ewing     Jan 13, 2008 in Science
An international study of 20,000 people found seven new genes that influence blood cholesterol levels, a major factor in heart disease, and confirmed 11 other genes previously thought to influence cholesterol.
Goncalo Abecasis is an associate professor in the U-M School of Public Health, and co-directed a study with Karen Mohlke, assistant professor of genetics at the University of North Carolina at Chapel Hill School of Medicine, that found seven new genes.
The study involved 20,000 people and the genes that were found all influence blood cholesterol levels, a major factor in heart disease, and confirmed 11 other genes previously thought to influence cholesterol.
The press release says that this was an international study and one that may lead the medical community to rethink the role of HDL (good cholesterol) and LDL (bad cholesterol) in heart disease.
"It was surprising that while genetic variants that increase your bad cholesterol are also associated with increased risk of heart disease, we did not find that variants influencing your good cholesterol were associated with decreased risk of coronary artery disease. Perhaps that result will lead us to reexamine the roles of good and bad cholesterol in susceptibility to heart disease," Abecasis said.
Coronary artery disease is a condition where plaque accumulates on the walls of coronary arteries and is the most common type of heart disease as well as a leading cause of death in industrialized countries.
It is the type and amount of cholesterol and other lipids in the bloodstream that contributes to the risk of coronary artery disease, which can cause heart attack, stroke, angina and other heart conditions. A person's cholesterol and blood lipid levels are influenced by both genetic and environmental factors.
"Finding new gene regions associated with cholesterol levels may bring us one step closer to developing better treatments, said Cristen Willer, co-first author and a research fellow in the Department of Biostatistics.ā€¯Nearly all of the gene regions that we found to be involved in higher LDL levels were also involved in coronary artery disease risk. This is a remarkable result and suggests that new drug therapies that target the genes in these regions will also help prevent coronary artery disease and allow people to live longer and healthier lives." Serena Sanna, who worked on the paper as a post-doctoral student in Abecasis' group and who is now at the National Research Council di Cagliari in Italy, is co-first author.
Of the seven new variants, two influenced HDL, one influenced LDL, and three influenced triglycerides. Triglycerides are found in fat and in the bloodstream and like LDL, are associated with increased risk of heart disease. One variant influenced triglycerides and LDL.
The researchers first examined 2 million genetic variants in 8,800 individuals and ended up focusing on a total of 25 genetic variants on 18 genes. Altogether the variations reported are responsible for less than a quarter of the genetic contributions to lipid levels.
The completion of the HapMap, or the map of human genetic variation, has fueled a surge in this type of genome-wide association study, with most of the growth coming in the past 10 months.
The research received major support from the National Human Genome Research Institute, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung and Blood Institute, all of which are part of the National Institutes of Health; the American Diabetes Association; the Department of Veterans Affairs; the British Heart Foundation; the United Kingdom's Medical Research Council; and the French Ministry of Higher Education and Research.
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