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Novel EU Pharmacogenomics Study Hopes to Learn Genetic Basis for Metabolic Syndrome

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A new European Union-funded study aims to explore how genetic variation and dietary fat consumption contribute to obesity and other risk factors for cardiovascular disease, which are known collectively as “metabolic syndrome.”

“The idea would be that we would gain information on which individuals are most susceptible to complications with the metabolic syndrome so … we are not wasting time treating people who won’t respond,” said Mike Gibney, a professor of nutrition at the department of clinical medicine at Trinity College in Dublin who heads the study.

The study, called Lipgene, costs €12.5 million ($15 million) and will be paid for by the EU. The research involves 24 centers in Europe and will run for five years. Besides examining the roles of genes and dietary fat in metabolic syndrome, the teams also plan to alter the fat composition in food such as linseed, milk, and poultry in order to make them more healthy.

To investigate how fats and genes influence metabolic syndrome — which comprise conditions such as obesity, hypercholesterolemia, insulin resistance, and hypertension — the researchers will re-analyze data from the control group of an eight-year French intervention study that involved 13,000 subjects.

The scientists plan to select 1,000 individuals from the control group who developed metabolic syndrome over the course of the study, called Suvimax, and 1,000 controls. The team will also genotype approximately 100 genes in order to look for polymorphisms that might influence the onset of metabolic syndrome in combination with dietary fat intake.

Among these genes will be those that affect lipid distribution, glucose disposal, and fatty acid metabolism. For example, it is known that people with a polymorphism in the PPAR gamma gene exhibit a change in insulin sensitivity when the ratio of dietary polyunsaturated to saturated fat is changed, said Gibney. Likewise, people with a common polymorphism in the ApoE gene do not respond to a low-fat diet, he said.

Hitachi will contribute to the study by analyzing genotype data using its Hitagene software, which was developed by bioinformaticists at Hitachi’s Dublin Laboratory, located at Trinity College. Hitagene can be used for linkage disequilibrium analysis, haplotype frequency estimation, and haplotype reconstruction, according to Hitachi.

Ultimately, the study could isolate a cluster of genes could emerge from the study that indicates a predisposition to metabolic syndrome, though there are no concrete plans yet to develop a diagnostic test, Gibney said. This could help decide who would benefit best from what kind of diet:

Another part of the project is a dietary intervention study slated to start early next year. The researchers will randomly assign a total of 480 people in eight cities to four diets and study whether they develop metabolic syndrome.

Variations in genes might explain why some subjects respond better than others to different diets, and help physicians put people on the diet that’s best for them: “In clinical nutrition, you are going to get much more personalized nutrition now,” Gibney said.

—JK

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