DNA May Provide Clues Towards Personalized Treatments for Metabolic Syndrome

Medical treatment is like solving a crime. Detectives use standard procedures to solve a puzzle: assess the scene, identify suspects and look for clues. For doctors, a disease can also be seen as a puzzle. They must assess the patient, identify risk factors and look for clues about how to best treat the problem. These clues can come in many forms. For most chronic diseases, some of these clues may be encoded in tiny variations in our DNA, which means that solving the puzzle may require a more personalized approach to treatment.

Metabolic syndrome (MetS) is one such disease. MetS is a group of health conditions that is associated with an increased risk of type 2 diabetes and cardiovascular disease. MetS is highly prevalent, affecting up to 40% of individuals in some populations. The syndrome is characterized by five major risk factors: obesity, elevated blood sugar, hypertension, elevated triglycerides (fats) and low high-density lipoproteins (HDL-cholesterol). Typically, MetS is diagnosed if a person has three or more of these risk factors. The first line of treatment for MetS involves lifestyle interventions using nutrition and exercise. But people can respond to these types of lifestyle interventions in very different ways, and patients are often left with little guidance.

A few years ago, the challenges associated with treating MetS sparked the launch of an innovative feasibility study known as the Canadian Health Advanced by Nutrition and Graded Exercise project, or CHANGE. CHANGE researchers provided 159 MetS patients with their own personal trio of experts: a physician, a nutritionist and an exercise physiologist. Rather than advising patients to generally improve their dietary and exercise habits with no further instruction, each patient was guided and monitored through a personalized, one-year lifestyle intervention. The overarching goal of the CHANGE program was to determine if a collaborative healthcare approach could improve the outcomes of MetS.

Along with healthcare professionals and researchers from Kingston, Laval, Edmonton and Toronto,  Prof. David Mutch in the Department of Human Health and Nutritional Sciences is part of the CHANGE team. Looking to see how genetics may have factored into the study’s outcomes, he and his research group carried out a genetic analysis of the patients who participated in the CHANGE project. Several graduate students in the Mutch lab have been involved in the CHANGE project since it first began, but the torch was recently passed to current MSc student Dana Lowry, a food enthusiast with a passion for personalized nutrition.

“I have always loved food and experimenting with my own diets, but I noticed that my friends and I might not respond to certain diets in the same way. I was intrigued by that ‘personalized’ aspect of nutrition,” says Lowry.

Lowry applied this personalized nutrition concept to the genetic analysis of the CHANGE participants. She noticed that some of the patients responded unfavourably, or saw no changes, in response to the lifestyle intervention.  She wondered if the variable response to lifestyle intervention could stem from underlying genetic differences.

To test her hypothesis, Lowry looked for relationships between individual responses to the CHANGE intervention and genetic differences known as  single nucleotide polymorphisms, or SNPs. SNPs are the small person-to-person differences in individual DNA building blocks (nucleotides) that make up a particular gene. Lowry sifted through SNPs identified in the participants’ genetic make up to determine if any of the observed differences were associated with their response to the lifestyle interventions.

Following her analyses, Lowry was able to identify variants in two genes that were consistently correlated to participants who responded poorly, or not at all, to the interventions. After searching the literature for putative functions associated with these genes, Lowry was able to speculate how they might be involved in MetS. The first gene, APOA-V, plays a role in moderating blood triglyceride levels. The second gene, ADIPOQ, encodes adiponectin, a hormone which regulates blood glucose levels and the breakdown of fatty acids. Lowry’s findings suggest that small variations in these genes may mediate how well a person responds to the CHANGE lifestyle intervention.

Because this study was conducted retrospectively, the next question Mutch and Lowry would like to ask is whether these genes can be used to predict treatment outcomes ahead of time.  They would also like to explore if particular interventions can be tailored to an individual’s specific genetic variant.

Studying the interaction between genes, nutrition and health is still in its infancy, but the healthcare world is increasingly intrigued by the possibilities of personalized nutrition. But before the genetic aspect of personalized lifestyle interventions could be implemented in a clinical setting, Mutch and Lowry caution that additional research is needed to determine how individuals might respond to receiving their own genetic profile, how to explain these genetic considerations to the public most effectively, and whether it will directly lead to positive health outcomes.

“At the end of the day there’s an equation that will probably predict a person’s response to an intervention, and the more factors we add to this equation, the closer we become to understanding these different responses,” says Mutch.

Perhaps in the future, collaborative healthcare clinics will involve physicians, nutritionists, exercise physiologists and geneticists.

This study was funded by Metabolic Syndrome Canada.

Read the full study in the journal Lifestyle Genomics.

Read about other  CBS Research Highlights.