Genomic Mapping Finds Cholesterol Genes
Nearly 100 Gene Variants Have Been Identified That Contribute to the Genetic Risk for High LDL Cholesterol, Including 59 New Ones
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Mapping Identifies LDL ‘Hotspots’ continued...
Two of the identified regions are already targets of existing cholesterol drugs, but many others had not previously been associated with cholesterol.
O’Connell tells WebMD that as many as several hundred more gene variants that help regulate cholesterol and triglyceride levels may be identified in the near future.
“We are beginning to understand the biology of lipids in a way that we never did before,” he says. “And new approaches for sequencing genes should help us find less common, but potentially more powerful, hot spots.”
Study Identifies LDL Protein
The investigation by Rader and colleagues focused on a region of chromosome 1p13 identified in the larger study.
For the first time a gene known as Sort1, which encodes a protein known as sortilin, was linked to the regulation of LDL cholesterol.
In studies in mice, the researchers were able to lower blood levels of LDL by dramatically lowering sortilin levels in the liver.
Rader says the Sort1 pathway may prove to be a new regulatory system for regulating cholesterol levels in humans.
“It makes sense that if we can figure out a way to tweak sortilin expression in a way that would reduce LDL in people, this would have a beneficial impact on heart disease risk,” Rader says.
The tricky part, he says, will be finding a way to lower LDL through this pathway without dramatically increasing sortilin in the liver.
“I’m not saying it’s going to be easy, but I do think this is a new pathway that has therapeutic potential.”
The study was partially funded through an American Recovery and Reinvestment Act grant.
O’Connell agrees the study by Rader and colleagues helps to validate the usefulness of large, ethnically diverse genomic mapping research.
“This type of research confirms the importance of large-scale, international collaborations in our attempt to discover the genetic underpinnings of disease,” he says.