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Study Suggests Adolescent Obesity and Genetic Factors Interact to Increase MS Risk

In a study comprising two large populations of people with MS and controls without MS, adolescent obesity was confirmed to increase a person’s risk for later developing multiple sclerosis, and this risk increased substantially in those with specific risk genes that control the immune system (known as HLA). Anna Karin Hedström, MD (Karolinska Institutet, Stockholm, Sweden) and colleagues in Sweden and California report their findings in Neurology (2014;82:1–8). More research is needed to confirm these results and to determine other risk factors that may help determine who is susceptible to MS and who is not.

Background: While MS is not contagious or directly inherited, epidemiologists—the scientists who study patterns of disease—have identified factors in the distribution of MS around the world that may eventually help determine what causes or triggers the disease. These factors include gender, genetics, age, geography, and ethnic background. The MS susceptibility genes identified to date are generally not clinically useful for providing genetic counseling to individuals regarding who may develop MS.

Because the prevalence of obesity has increased dramatically in the past several decades, and obesity is associated with an increase in immune system activity, researchers are seeking to determine if there was any association between obesity and the risk for developing MS.

Researchers recently reported that being overweight or obese was associated with an increased risk of developing MS or clinically isolated syndrome (CIS, a first clinical episode suggestive of MS, indicating increased MS risk) in girls, in a study that compared 75 children or teens with MS or CIS with the health records of more than 900,000 healthy children or teens (Neurology February 5, 2013 80:548-552).

The Study: Investigators used data from two studies on environmental and genetic risk factors, analyzing two populations: one that had 1,510 cases of MS and 2,017 controls without MS and another that comprised 937 cases and 609 controls. They obtained information on two genes previously associated with MS risk (the presence of “HLADRB1*15,” thought to increase MS risk, and absence of “HLA-A*02,” thought to be protective against MS), body mass index at age 20, and development of MS.

In both study populations, adolescent obesity was associated with increased risk of MS, as was the presence of HLADRB1*15or the absence of HLA-A*02. Participants who showed both adolescent obesity and either of the genetic risk factors had nearly an eight-fold increased risk of developing MS compared to those who were not obese in adolescence and who did not have any of the genetic risk factors.  However those who reported adolescent obesity and both of the genetic risk factors had a 16-fold or 14-fold increase in risk of MS.

Conclusions: This study adds to the growing body of evidence that adolescent obesity is a risk factor for developing MS. The authors note that “biologic explanations are far from clear,” but they suggest that immune mechanisms associated with obesity may be active in driving the disease in people who are genetically susceptible. Additional research is needed to understand this association. It is important to note that not everyone who is obese during adolescence will develop MS, and also that many people develop MS without having been obese during adolescence.

“We should be concerned about these findings,” cautions Ruth Ann Marrie, MD, PhD (University of Manitoba, Winnipeg, Canada) and Christopher A. Beck, PhD (University of Rochester Medical Center, NY) in an accompanying editorial. “It is time to begin developing a targeted approach to prevent MS by improving common health behaviors, including body weight and smoking.”

About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.