Mediterranean Diet May Reverse Genetic Risk for Stroke

Pauline Anderson

August 20, 2013

Following a Mediterranean diet (MedDiet) may not only reduce fasting glucose concentrations and lipid levels in patients who are genetically at increased risk for type 2 diabetes but may also lower their risk for stroke, a new study suggests.

Polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene are strongly associated with type 2 diabetes, as well as, in some studies, plasma lipids and cardiovascular disease. In this study, researchers looked at whether the MedDiet, which features olive oil, nuts, fish, whole grains, fruits, vegetables, and healthier fats, could moderate the genetic risk for cardiovascular outcomes associated with one of these polymorphisms, TCF7L2-rs7903146.

"Being on the Mediterranean diet reduced the number of strokes in people with 2 copies of the variant," said study author José M. Ordovás, PhD, professor, Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, in a press release. "The food they ate appeared to eliminate any increased stroke susceptibility, putting put them on an even playing field with people with one or no copies of the variant."

The study results "support the benefits of a MedDiet, especially for genetically susceptible individuals and emphasize the importance of studying entire dietary patterns rather than individual components," the authors, led by Dolores Corella, PhD, Department of Preventive Medicine and Public Health School of Medicine, University of Valencia, Spain, conclude.

The study was published online August 13 in Diabetes Care.

Genetically Susceptible

This analysis included 8018 older men and women entered in the PREvención con DIetaMEDiterránea (PREDIMED), a multicenter clinical trial aimed at assessing the effects of the MedDiet on the primary prevention of cardiovascular disease. Patients in the study had type 2 diabetes or at least 3 cardiovascular risk factors, such as hypertension, dyslipidemia, obesity, or smoking.

Previous reports from the PREDIMED study have shown that this diet reduced carotid plaque, improved cognitive function, reduced cardiovascular events by about half, and also halved new-onset type 2 diabetes vs the low-fat arm of the study during the trial.

For this analysis, DNA was extracted from these patients and genetic variation in TCF7L2-rs7903146 was determined. About 14% of the participants were homozygous carriers, meaning they carried 2 copies of the TCF7L2 gene variant, a group referred to as TT.

Study patients were randomly assigned to the MedDiet supplemented with extra-virgin olive oil, to the MedDiet supplemented with mixed nuts, or to a control group that followed a low-fat diet. The groups were followed for a median of 4.8 years.

As expected, the TCF7L2-rs7903146 polymorphism presented a highly significant association with type 2 diabetes at baseline. Researchers also noted a highly significant association (P < .001) between this polymorphism and increased fasting glucose, although the statistical significance was lessened after adjustment for type 2 diabetes.

Their results showed significant gene-diet interactions. When adherence to the MedDiet prior to randomization in PREDIMED was low (below sample mean of 9 points), patients carrying the TT genotype had higher fasting glucose concentrations than those with other genetic variations (132.3 vs 127.3 mg/dL; P = .001). When adherence to the diet was high (≥9 points), there was no such increase.

This modulation by diet was also detected for total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels.

Stroke Risk

During the study period, 262 major cardiovascular events occurred, including 130 strokes.

When adherence to the MedDiet was low, TT patients presented a higher risk for stroke than those with other genetic variants (hazard ratio [HR] in the adjusted model that included diabetes, 2.44; 95% confidence interval [CI], 1.26 - 4.72). No higher risk was found when adherence to the MedDiet was high (HR, 0.99; 95% CI, 0.44 - 2.22).The mechanism of this effect is unknown, said the authors.

Importantly, the study showed that in the low-fat control diet, homozygous carriers were almost 3 times as likely to have a stroke as people with 1 or no copies of the gene variant (adjusted HR, 2.91; 95% CI, 1.36 - 6.19; P = .006).

Because modulation of stroke incidence by the MedDiet was similar in the group that received the diet supplemented with olive oil and the one supplemented with nuts, "our results suggest once again that it is the overall MedDiet pattern rather than specific foods that contribute to not increasing stroke risk in TT individuals," said the authors.

"Our study is the first to identify a gene-diet interaction affecting stroke in a nutrition intervention trial carried out over a number of years in thousands of men and women," commented Dr. Ordovás in the release. "The PREDIMED study design provides us with stronger results than we have ever had before. With the ability to analyze the relationship between diet, genetics, and life-threatening cardiac events, we can begin to think seriously about developing genetic tests to identify people who may reduce their risk for chronic disease, or even prevent it, by making meaningful changes to the way they eat."

Although the study's sample size was large, the interactive findings of stroke risk with the MedDiet rest on relatively few stroke cases, the authors point out.

This study was funded by the Spanish Ministry of Health (Instituto de Salud Carlos III), the Ministry of Economy and Innovation, Fondo Europeo de Desarrollo Regional, and contracts from the U.S. Department of Agriculture Research Service, and the Generalitat Valenciana. The authors have disclosed no relevant financial relationships.

Diabetes Care. Published online August 13, 2013. Abstract

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