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  • May 24 2011

    Personalized health and gene-behavior interactions: The case of HDL-cholesterol and exercise

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    "In the clinic, if somebody has low HDL-cholesterol levels, the first thing I tell them is to get out and exercise. But genetic loci have been identified that affect HDL-cholesterol levels as well. The question is, how do these two factors work together, or work against one another, to alter HDL-cholesterol levels?" - Brendan Everett, Brigham and Women's Hospital, Harvard University

    ahmadCommon genetic variants that influence HDL-cholesterol levels are modulated by how physically active you are, according to the results of a new study conducted by Harvard and Duke (link below). The beneficial effects of exercise on HDL-cholesterol were greates for those who have SNP polymorphisms in hepatic lipase (LIPC) and cholesteryl ester-transfer protein (CETP) genes, and, for those who do have these polymorphisms, among those who exercised more than 8.8 MET-hours-per-week. For the rs10096633 polymorphism in the lipoprotein lipase (LPL) gene, women who exercised a lot had a smaller gain in HDL-cholesterol ("good cholesterol") than the less-active women experienced.

    This was a prospective cohort study of 22,939 healthy women of European ancestry, age 45 years or older, studied between 1995 and 2008, not just measuring lipid levels but survival and cardiac and other outcomes as well.

    In active individuals--defined as exercising more than 8.8 MET-hours-per-week--the increases in HDL cholesterol per copy of the minor-allele increases for LIPC (rs1800588) and CETP (rs1532624) were larger than in those who exercised less. The reverse, however, was observed with LPL.

    About 60% of people of European descent have at least one copy of 'T' at rs1800588. (You can look at the proportions for different races by clicking on links below.) About 70% of people of European descent have at least one copy of 'T' at rs1532624 ('A' on the 23andme microarray chip, since that uses opposite DNA strand-orientation compared to NIH's dbSNP database).

    And about 25% of people of European descent have at least one copy of 'T' at 10096633. So the prevalence of these variations is common enough to really matter for a large proportion of people, with regard to the benefits that regular exercise can have for them on lipid levels and cardiovascular risk.

    If you've had one of the direct-to-consumer (DTC) genomics tests done (such as 23andme), you can figure your own situation out, DIY-style, by browsing your genotypes at these SNPs in the raw file download results.

    By doing this and finding out that moderate amounts of exercise is, for you and given your specific genomic variations, likely to improve your "good cholesterol" more than it would for the "average" person... is one personalized kind of encouragement, adding to your motivation to do the healthy exercise thing.

    Douglas McNair, MD PhD, Senior VP, is one of three Cerner Engineering Fellows and is responsible for innovations in decision support and very-large-scale datamining. McNair joined Cerner in 1986, first as VP of Cerner's Knowledge Systems engineering department; then as VP of Regulatory Affairs; then as General Manager for Cerner's Detroit and Kansas City branches. Subsequently, he was Chief Research Officer, responsible for Cerner's clinical research operations. In 1987, McNair was co-inventor and co-developer of Discern Expert®, a decision-support engine that today is used in more than 2,000 health care facilities around the world. Between 1977 and 1986, McNair was a faculty member of Baylor College of Medicine in the Departments of Medicine and Pathology. He is a diplomate of the American Board of Pathology and the American Board of Internal Medicine.

    Additional resources:

    Ahmad T, et al. Physical activity modifies the effect of LPL, LIPC, and CETP polymorphisms on HDL-C levels and the risk of myocardial infarction in women of European ancestry. Circ Cardiovasc Genet 2011; 4: 74-80. Abstract (download supplemental material)

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