Malaga researchers discover 'genetic signature' that predicts success rate of bariatric surgery

Between 7% and 25% of patients with obesity who undergo bariatric surgery do not achieve the expected goals: they either lose fewer kilos or remain at the weight they had before the operation. A group of researchers from the biomedical research institute of Malaga (IBIMA-Plataforma Bionand), specifically from the group obesity, diabetes and its comorbidities: prevention and treatment group, led by IBIMA scientific director Dr Francisco J. Tinahones, have identified several genetic biomarkers that can predict the response that a patient would have to these interventions, which could "revolutionise" the personalisation of treatments for obesity.

Obesity has now become a 21st-century illness, with a much greater complexity than is commonly thought and with numerous factors that cause it. It affects millions of people around the world. It is estimated that 20% of the Spanish population suffers from this pathology, which is often accompanied by a kind of stigma and social reproach that doctors and experts themselves are trying to combat. That is why experts are changing the language surrounding the issue. According to IBIMA-Plataforma Bionand, bariatric surgery has proven to be effective "in achieving sustained weight loss". Understanding why some patients lose weight and others do not is essential to optimising clinical outcomes.

DNA methylation is an epigenetic modification, i.e. a change in the chemical structure of DNA that does not alter its coding sequence. Several previous studies have considered that this gene methylation may influence the development of metabolic diseases and the response to weight loss interventions, but its role as a potential predictor of the success of bariatric surgery had not been established until now.

Researchers analysed blood samples from 20 people before they underwent tummy tuck surgery (abdominoplasty). One year later, they found that one group of people had lost more than 60% of their excess weight, while other patients had not. By comparing DNA methylation profiles, the researchers detected more than 76,000 differences in small chemical markers in the DNA (methylations) which, in turn, could determine a patient's response after surgery.

This suggests that the assessment of DNA methylation in the blood before a patient undergoes the surgery could help predict their individual response to this intervention, personalising physicians' treatment and follow-up strategies and ensuring greater efficacy in the approach.

Of all the markers analysed, three stood out for their ability to predict outcomes. "We found that higher DNA methylation at specific sites in the HOXA5 gene is associated with a lower probability of successful weight loss, while higher methylation in JAK2 is associated with better outcomes," says Dr Sonsoles Morcillo, one of the lead researchers in the study. In other words, DNA could hold, at least partially, the key to predicting the results of this type of surgery, opening the door to more personalised treatments.

Dr Gutiérrez-Repiso stresses that these biomarkers help experts move towards "more personalised medicine in the treatment of obesity". Lead study author Guillermo Paz-López calls for "further studies with larger samples" that would be "needed to validate these results".