August 5, 2010

Scientists Pinpoint 95 Gene Loci Linked To Lipid Metabolism

Discovery may offer new approach to treating coronary artery disease

Together with their colleagues from the Global Lipids Genetics Consortium, scientists of Helmholtz Zentrum Mnchen have found 95 gene loci in the human genome, each of which is associated with at least one of the four most important factors of lipoprotein metabolism: total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides.

The study focused, along with other aspects, on two key questions: First, are there really genes on these loci that directly influence lipoprotein metabolism? Second, do they have any significance for possible therapy approaches? The scientists were able to answer both questions with a clear yes: "By means of this analysis we even succeeded in pinpointing genetic variants associated not only with elevated lipid levels but also with coronary artery disease," explained Dr. Christian Gieger of the Institute of Epidemiology at Helmholtz Zentrum Mnchen.

"It is often argued that large-scale meta-analyses with more than 100,000 test subjects have little significance for the biology of complex diseases. Our study impressively refutes this assertion," said Professor H.-Erich Wichmann, director of the Institute of Epidemiology at Helmholtz Zentrum Mnchen. "On the contrary, some of the newly discovered gene loci have clear biological and clinical relevance."

Professor Thomas Meitinger, director of the Institute of Human Genetics at Helmholtz Zentrum Mnchen, which also participated in the study, added: "Closer scrutiny of the gene loci revealed genetic variants which we know offer a molecular target for cholesterol-lowering drugs. That means that these genetic variants raise the potential for new target structures and thus new therapeutic approaches.

Data from 46 genome-wide association studies including more than 100,000 individuals were used in this meta-analysis. One important data source was the population-based study KORA (KORA = Cooperative Health Research in the Region of Augsburg) of Helmholtz Zentrum Mnchen. The scientists used a variety of methodical approaches: For instance, they compared more than two and one-half million DNA building blocks from population groups of European and non-European origin, analyzed genetic variants of patients with extreme lipid concentrations and confirmed some of their own findings from the genome-wide analysis in mouse models.

Cardiovascular diseases are still the leading cause of death in Germany. Almost one in two deaths in Germany can be traced to a disease of the cardiovascular system. Elevated blood lipid levels are among the most important risk factors for heart diseases. The present findings confirm the association of genetic variations with blood lipid levels and cardiovascular diseases.


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