Fat Plus SNP Fights Metabolic Syndrome

Patients with metabolic syndrome who have a certain gene variant may benefit more from a high-fat diet than a low-fat one, researchers found.

In a randomized, controlled trial, patients with the single nucleotide polymorphism (SNP) rs1522813 in the insulin receptor substrate-1 (IRS1) gene had a significantly greater chance of having metabolic syndrome resolve if they were on a high-fat diet (OR 2.88, 95% CI 1.25 to 6.67,P=0.04), according to Lu Qi, MD, PhD, of Harvard School of Public Health, and colleagues.

It's not clear why a high-fat diet interacts with this genotype for better results, and further study is needed, the researchers reported online in Diabetes Care.

They had previously reported that their study, the POUNDS LOST trial, showed that diets varied in fat and carbohydrate content were similarly effective in reducing metabolic syndrome in overweight or obese patients over a 2-year period.

But other work has suggested that genetic variants near IRS1 are associated with features of the metabolic syndrome. So to explore whether these SNPs modulate the effects of various diets on metabolic syndrome, Qi and colleagues genotyped the 738 overweight and obese patients enrolled in the trial for two variants: rs1522813 and rs2943641.

Among patients with the rs1522813 genotype, those on a high-fat diet had higher reversion rates of metabolic syndrome than those on a low-fat diet at 2 years (45.9% versus 28.1%,P=0.04).

Patients without this variant had no difference in reversion rates whether their diet had a high or low fat content.

In regression analyses, the high-fat diet was also significantly associated with reversion of metabolic syndrome among those with the variant (OR 2.88, 95% CI 1.25 to 6.67, P=0.04).

On the other hand, the variant rs2943641 didn't modulate dietary effects on metabolic syndrome.

"It is possible that this genetic variant might be more related to weight loss and insulin resistance in response to dietary intervention, while the genetic variant rs1522813 is more likely to interact with dietary intervention on changes in blood pressure, plasma HDL cholesterol, and triglycerides," Qi and colleagues wrote.

They noted that the genetic influence on dietary effects was independent of weight changes, suggesting that the genotype-diet interaction on resolution of metabolic syndrome may be less influenced by changes in adiposity -- potentially indicating a "stable and long-term modification effect" of this SNP on reversal of metabolic syndrome in response to diet.

"Our data may provide useful information to the development of dietary interventions in the management of the metabolic syndrome based on genetic background," they wrote.

It's still not clear why the high-fat diet interacts with this genotype for better metabolic results, and needs further investigation, Qi and colleagues concluded, noting, however, that high-fat diets involve fewer carbohydrates, which could play a role in the effect.

This article was obtained from MedPage Today for educational purposes only.

Nutrigenomics, Diet and Disease