NEW YORK – A team led by researchers at the University at Buffalo in New York is investigating whether a genetic test originally developed to predict susceptibility to addiction can also help physicians better prepare obese patients for bariatric surgery.
Previous research has implicated about a dozen genetic variants that can predispose individuals to addictive behaviors. Based on one-year results from an ongoing longitudinal study, some of those same genes may be able to predict how patients will fare after bariatric surgery and their likelihood of maintaining weight loss.
Those risk alleles may be able to provide physicians with actionable information about patients before surgery, said Panayotis Thanos, a senior research scientist in the pharmacology and toxicology department at the University at Buffalo's Jacobs School of Medicine and Biomedical Sciences. Thanos spent the last 15 years studying the underlying common mechanisms between obesity and addiction and is also leading the latest research at the university on using genetics to predict bariatric surgical outcomes.
Thanos suggested that once these genetic variants are validated, testing patients for them could help physicians identify those who might need additional help to sustain weight loss after bariatric surgery, such as through pre-procedure counseling, behavioral follow-up, or other supportive measures.
However, he cautioned that such a genetic test isn't ready to be used in patient care yet. "We're at the beginning right now," Thanos said. "We still need more research to validate and expand [understanding of the variants] before we can recommend it."
For the past two decades, the prevalence of obesity in the US has consistently grown, creating a market for bariatric surgical procedures that can help patients with severe obesity reduce their weight by making adjustments to their digestive systems. Gastric sleeve and bypass surgery, for example, are types of bariatric surgery that physically restrict a patient's food intake.
Bariatric surgery is considered an effective treatment for severe obesity in patients who haven't been able to lose weight with diet and exercise. However, not all patients experience positive outcomes. Prior studies in which researchers tracked patients for more than five years post-procedure showed that up to three-quarters of individuals who underwent sleeve gastrectomy had clinically significant weight regain. And patients already susceptible to addictive or compulsive behaviors might be at risk of developing new poor habits, such as alcohol abuse or gambling, in lieu of overeating, Thanos noted.
To better understand whether certain genetic variants can predict weight loss outcomes, Thanos and colleagues enrolled nearly three dozen patients undergoing bariatric surgery at Kaleida Health's Buffalo General Medical Center into a study. They asked patients to provide a cheek swab sample for genetic risk assessment and fill out questionnaires assessing psychosocial factors related to eating habits. Researchers analyzed patients' samples using the Genetic Addiction Risk Severity (GARS) assay developed by research collaborator Kenneth Blum. A neuropharmacology researcher, Blum is known for coining the term "reward deficiency syndrome" to describe people's behavioral response to dopamine resistance. The GARS test analyzes 11 genetic variants linked to release of dopamine, serotonin, and other neurotransmitter systems.
In a potentially unexpected twist, after one year, patients deemed to have a high genetic susceptibility to addiction were more likely to experience sustained weight loss post-surgery, compared to those without the genetic variants.
In an analysis of 30 patients with one-year follow-up data, investigators reported in Biomedicines this fall that a patient's GARS score was correlated with percentage of expected weight loss, change in weight, and change in body mass index. This suggested that patients predicted to have a strong genetic predisposition to addiction are also more responsive to weight loss surgery.
"At first glance, it may seem contradictory that individuals with a genetic susceptibility to addictive eating and obesity would have such a positive response to bariatric surgery," study authors wrote in the paper. They hypothesized that the surgical procedures normalized dopamine D2 receptors that were previously disrupted in patients with the risk alleles.
In particular, patients with the rs1800497 variant in the DRD2 gene, which earlier research has shown to be linked to obesity and addictions like alcoholism, were more responsive to weight loss treatment and maintained weight loss compared to those without it. The OPRM1 rs1799971 variant, too, was associated with improvements to weight and BMI after one year, according to the paper.
The findings build on results from a separate study from the research team, published in the Journal of Personalized Medicine over the summer, in which investigators reported six-month weight loss outcomes. In that paper, investigators found that, based on genetic risk scores, three-quarters of patients had elevated risk for alcohol use disorder — suggesting many patients could benefit from counseling about alcoholism as part of their care plans.
The research findings add to a growing body of data around the complexity of genetics and their effect on obesity, and it's encouraging that patients with a particular allele responded well to surgery, said Marina Kurian, a physician and president of the American Society for Metabolic and Bariatric Surgery, who was not involved in these studies. But while the research is promising, Kurian agreed that it's too early to bring into clinical care.
"Correlation of these genetic findings with measures to improve outcomes will be the future," she wrote in an email, adding that not all patients who have obesity have addictive aspects to their dietary regimen. "Obesity is such a multifactorial disease that this will ultimately be one piece of a greater puzzle."
She said she hopes to see additional long-term investigations into whether patients with different genetic profiles benefit from particular procedures and other weight loss treatments.
The team led by University at Buffalo researchers will continue to track patients to assess longer-term outcomes and whether they develop new addictive behaviors two years post-surgery, Thanos said. Those findings will inform a larger study that the team hopes to launch at multiple sites, in which they will track patients for even longer.
"We hope to learn more as these subjects go on further out in terms of their recovery," Thanos said. "If a subject does have a negative outcome, like regaining the weight, that's going to tend to happen further past the surgery."