Study Links FTO Gene Mutation to Obesity, Increased Disability in MS Patients

A common mutation in the fat-mass obesity (FTO) gene is associated with obesity and increased disability in people with multiple sclerosis (MS), according to a Kuwaiti study.

The data, which showed no link between this mutation and an increased risk of MS, highlights the need for more studies about the role of FTO in MS progression in order to determine the best therapeutic interventions in patients carrying this mutation.

The study, “The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients,” was published in the journal Nature Scientific Reports.

MS is caused by a combination of genetic and environmental factors. Several studies have suggested that obesity increases the risk of developing MS, and is associated with increased MS disability and progression.

While the underlying mechanisms of obesity’s contribution to MS remain unclear, evidence points to obesity-related chronic low-grade inflammation and release of immune-related molecules and changes in the central nervous system (spinal cord and brain).

Previous studies have associated the presence of a common mutation in the FTO gene — called rs9939609 — with obesity in several populations. The exact role of the FTO protein is unknown, but researchers believe it is involved in the regulation of fat production and energy balance, as well as in nerve cell development and food-craving behavior.

The link between rs9939609 FTO mutation and obesity, as well as between obesity and MS risk, suggest that the mutation may have a role in MS development, and be the underlying mechanism linking obesity and MS. However, there is limited data on FTO mutations in MS patients and how they may be associated.

Researchers set out to evaluate the potential link of this FTO mutation with overweight/obesity, MS risk, and MS-related disability in Kuwaiti MS patients. The mutation previously had been associated with obesity in the Kuwaiti population.

The team recruited and analyzed data from 200 people with MS (135 women and 65 men, average age 32.3 years) at the Dasman Diabetes Institute’s MS clinic, as well as from 206 healthy volunteers (125 women and 91 men, average age 52.3 years).

Body-mass index (BMI) was used to determine people’s weight status (underweight, normal weight, overweight, and obese). Patients’ disability was measured using the MS-validated Expanded Disability Status Scale (EDSS).

Analyses of potential associations were conducted considering two genetic models. The co-dominance model, in which the increasing number of mutated gene copies, from zero to two, increases the mutation’s effect; and the recessive model, in which the mutation’s effect takes place only when the mutation is present in both gene copies.

After adjusting for both age and gender, results showed that MS patients carrying the FTO mutation had a significantly increased risk of being overweight or obese, compared with those who did not. This was true for both genetic models.

Interestingly, there were no significant differences in the frequency of the FTO mutation between the two groups (MS patients and controls), suggesting that the mutation was not associated with an increased risk of developing MS.

Researchers noted that the results were consistent with the data of the only other study evaluating the potential association between this FTO mutation and MS risk in people living in South Africa.

However, the analysis revealed that carrying the mutation was associated significantly with increased MS disability in both genetic models, even after adjusting for age, gender, BMI, and disease duration.

The team noted that this association may be explained by the FTO’s involvement in food-craving behavior, as well as in the balance between lean muscle and fat mass.

“Lower cognitive restraint [in food intake] may impact an already poor lean muscle mass in these patients, reducing their inclination to perform physical exercise”, the researchers wrote, adding that less physical activity and higher body fat have been shown “to directly impact disability in MS patients.”

“Our association with obesity is consistent with previous reports, whereas the association with disability is novel and warrants further investigation on the role of FTO in disease progression,” the researchers noted.

According to the team, larger studies are required to confirm these results, and determine the association between this FTO mutation and MS progression. The team emphasized that this will be important to understand whether MS patients carrying the mutation should be encouraged to counteract food cravings and lack of commitment toward physical activity to improve their disease course.