Nutrition researchers at Washington University School of Medicine in St. Louis have identified five 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.
People with metabolic syndrome have at least three of the following symptoms: abdominal obesity, high blood triglyceride levels, lower good cholesterol (HDL), elevated blood pressure and elevated fasting blood glucose. They are four times as likely to develop heart disease and at least seven times more likely to develop diabetes as individuals without metabolic syndrome.
The investigators, who report 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 to the risk for metabolic syndrome and abnormal levels of good cholesterol is important because as more people in the United States become obese, they also become susceptible to these problems. Better understanding of the relationships between obesity, the gene and disease risk may allow for earlier identification of individuals who are more susceptible to develop metabolic syndrome. Treatments such as medication or lifestyle changes could begin earlier, perhaps preventing or delaying future problems with diabetes or heart disease.
Senior investigator Nada A. Abumrad, Ph.D., the Dr. Robert C. Atkins Professor of Medicine and Obesity Research, first identified the CD36 protein in studies with mice. Her research has demonstrated that the protein facilitates the use of fatty acids for energy. CD36 is located on the surface of cells and distributed throughout many tissues, including fat cells, the digestive tract, heart and skeletal muscle.
The investigators - who included M. Alan Permutt, M.D., professor of medicine and of cell biology and physiology; Rosalind J. Neuman, Ph.D., professor of mathematics in psychiatry; and Samuel Klein, M.D., the Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition - focused on 36 small genetic variations, called single nucleotide polymorphisms (SNPs), in the CD36 gene. A SNP involves a single base-pair change in the DNA.
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 researchers expect, however, that these findings also will be applicable in other populations.
"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.
Love-Gregory says the research team demonstrated an association between SNPs in the gene and metabolic syndrome.