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Jun 18, 2008

Gene Variants Linked to Metabolic Syndrome and HDL Cholesterol Levels Identified

  • Researchers at Washington University School of Medicine in St. Louis have identified five common genetic variations that increase the risk of metabolic syndrome. Another variant they found appeared to protect against the condition.

    The investigators, who reported their findings in the June issue of 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 team evaluated DNA taken from more than 2,000 African-Americans because variations in the gene are more common in individuals of African and Asian descent than in other racial groups.

    "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, Ph.D., research instructor in the division of geriatrics and nutritional science.

    Dr. Love-Gregory says the research team demonstrated an association between 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 explains. "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 five of the SNPs they examined are more common in people who have symptoms of metabolic syndrome, but a sixth seemed to have a more favorable metabolic effect. The protective SNP makes people produce lower amounts of CD36 protein.

    In this study, people who had the protective variant on only one of their copies of chromosome 7 were less susceptible to metabolic syndrome. But people with two 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.

    The researchers 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 isn't 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."

    Related Links:

    NAFLD and NASH Linked to Metabolic Syndrome and Cardiovascular Disease

    Scientists Link Oxidation of LDL to Metabolic Syndrome

    Target Identification Methods Advance



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