January 14, 2008 -- ANN ARBOR, Mich.---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.
The
international study led by researchers from the University of Michigan
School of Public Health set out to identify or confirm genetic variants
that influence lipid levels, and secondly, to see if those variants
were linked to the decreased or increased risk of heart disease. The
findings will be published online in the journal Nature Genetics on
Jan. 13.
The results may lead the medical community to rethink the role of HDL
(good cholesterol) and LDL (bad cholesterol) in heart disease, said
Goncalo Abecasis, associate professor in the U-M School of Public
Health. Abecasis co-directed the study with Karen Mohlke, assistant
professor of genetics at the University of North Carolina at Chapel
Hill School of Medicine.
"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, a
condition where plaque accumulates on the walls of coronary arteries,
is the most common type of heart disease and a leading cause of death
in industrialized countries. The type and amount of cholesterol and
other lipids in the bloodstream contribute to the risk of coronary
artery disease, which can cause heart attack, stroke, angina and other
heart conditions. Both genetic and environmental factors influence a
person's cholesterol and blood lipid levels.
"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. "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, which 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.
Scientists initially 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 map of human genetic
variation, or HapMap, has fueled a surge in this type of genome-wide
association study, with most of the growth coming in the past 10
months. Researchers around the globe have now associated more than 60
common DNA variants with the risk of more than 20 common diseases or
related traits.
Source : University of Michigan
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