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Title: Gene Variants Linked to Metabolic Syndrome and HDL Cholesterol Levels
URL: http://www.pslgroup.com/dg/223C9E.htm
Doctor's Guide
June 18, 2008

ST. LOUIS, Missouri -- June 18, 2008 -- Nutrition researchers at Washington University School of Medicine in St. Louis have identified 5 common genetic variations that increase the risk of metabolic syndrome, a group of factors linked to heart disease and diabetes. Another variant they found appeared to protect against the condition.

The investigators, who reported their findings in the June issue of the journal Human Molecular Genetics, looked for changes in the CD36 gene, which is located in a region of chromosome 7 that has been linked to metabolic syndrome in several genome-wide studies.

The researchers say linking changes in the CD36 gene increase the risk for metabolic syndrome and abnormal levels of high-density lipoprotein (HDL) cholesterol. Better understanding of the relationships between obesity, the gene, and disease risk may allow for earlier identification of individuals who are more susceptible to developing metabolic syndrome. Treatments such as medication or lifestyle changes could begin earlier, perhaps preventing or delaying future problems with diabetes or heart disease. The team evaluated DNA taken from more than 2,000 African Americans.

"The idea was to look at the different variations in the gene and see whether they were more prevalent in people who also had elevated cholesterol, abnormal blood glucose, or the other components of the metabolic syndrome," says first author Latisha Love-Gregory, PhD, Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri.

Dr. Love-Gregory says the research team demonstrated an association between single nucleotide polymorphisms (SNPs) in the gene and metabolic syndrome.

"There is additional work to do to determine if the function of these genetic variants actually contributes to the development of type 2 diabetes or heart disease," she explained. "We do expect that a number of different changes, in both CD36 and other genes, will be related to these diseases. What we'd like to learn, however, is whether the changes identified in the gene alter the CD36 protein in ways that change its function to make a person more vulnerable."

The team determined that 5 of the SNPs they examined are more common in people who have symptoms of metabolic syndrome, but a sixth seemed to have a more favourable metabolic effect. The "protective" SNP makes people produce lower amounts of CD36 protein.

In this study, people who had the protective variant on only 1 of their copies of chromosome 7 were less susceptible to metabolic syndrome. But people with 2 copies of the variant, who were completely deficient in the CD36 protein, did not appear to be protected. They tended to have lower levels of HDL.

"A bit less CD36 protein may improve your risk profile, but people need some CD36 function," the researchers said.

Dr. Love-Gregory found that many variants influenced blood levels of HDL cholesterol. Now they are taking a closer look at the relationship between CD36 and HDL cholesterol. Higher levels of HDL normally are considered positive, but because changes in the CD36 gene seem to influence HDL, the researchers want to make sure that the HDL molecule is not being altered in composition or function.

"We're going to follow up on the HDL component of the study," Dr. Love-Gregory says. "We're also going to look for additional variants in the promoter region of the gene that controls how the gene is regulated. And we're planning to look for evidence of these gene variants and their associations with HDL and the metabolic syndrome in other populations and ethnic groups."


SOURCE: Washington University School of Medicine

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