Five common genetic variations increase risk for developing metabolic syndrome, while another variation appears to decrease risk for the condition, according to an article in the June issue of Human Molecular Genetics.

Diagnosis of metabolic syndrome requires at least three of the following: abdominal obesity, high blood triglyceride levels, low high-density lipoprotein cholesterol, hypertension, and elevated fasting blood glucose. Affected individuals are four times as likely to develop heart disease and at least seven times more likely to develop diabetes as individuals without metabolic syndrome.

In the current work, investigators looked for changes in sequence of the CD36 gene, which has been linked to metabolic syndrome in several genome-wide studies.

The researchers wrote that an improved understanding of the relationships between obesity, genotype, 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.

Senior investigator Nada A. Abumrad, PhD, the Dr. Robert C. Atkins Professor of Medicine and Obesity Research at Washington University School of Medicine, first identified the CD36 protein in studies with mice. Her research demonstrated that the protein facilitates the use of fatty acids for energy.

The investigators focused on 36 single nucleotide polymorphisms in the CD36 gene. The team evaluated DNA 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," said lead author Latisha Love-Gregory, PhD, research instructor in the Division of Geriatrics and Nutritional Science.

The team determined that five of the variations they examined were more common in people with symptoms of metabolic syndrome, but a sixth seemed to have a more favorable metabolic effect in heterozygous individuals. The "protective" variation makes people produce lower amounts of CD36 protein.

The researchers found that many variations influenced blood levels of high-density lipoprotein cholesterol. Current work is examining the relationship between CD36 and high-density lipoprotein cholesterol (HDL). Higher levels of HDL normally are considered positive, but because changes in the CD36 gene seem to influence levels, the researchers want to make sure that the HDL molecule isn't being altered in composition or function.