Adolescent Obesity and HLA Genotype Linked to Increased Risk of Multiple Sclerosis

multiple sclerosis and ObesityA number of factors are associated with an increased risk of developing adult-onset multiple sclerosis (MS), including modulated immune function, vitamin D insufficiency, the human leukocyte antigen (HLA) genotype, and interaction with the Epstein-Barr virus. Interestingly, some of these risk factors are also associated with being obese. Since obesity is also associated with low-grade chronic inflammation, it is projected that the risk of HLA-related activation of T-cells contributes to an autoimmune attack on the central nervous system, leading to MS. Dr. Anna Karin Hedström from the Karolinska Institutet in Sweden, along with colleagues from other institutes including the University of California, Berkeley, to investigate the link between adolescent obesity and HLA genes in the development of multiple sclerosis; results were published in Neurology.

Two case-control studies were conducted: the Epidemiological Investigation of MS (EIMS) study included 1,510 incident cases of MS, and the Kaiser Permanente Medical Care Plan in Norther California (KPNC) study included 937 prevalent cases of MS. Each patient, along with matched controls, was genotyped for HLA-DRBI*15 and HLA-A*02, and body mass index (BMI) at the age of 20 years was self-reported.

When odds ratios (OR) were analyzed, it was found that obesity (defined as a BMI of 27 or greater) in adolescence increased the risk of MS in both studies by an OR of approximately 2. Furthermore, there was an interaction between adolescent obesity and HLA-DRBI*15 with respect to MS risk: the OR of an obese participant with the allele was 7.9-fold higher than the OR of a non-obese participant without the allele in the EIMS study (KPNC found a similar interaction). HLA-A*02 showed a greater interaction with adolescent obesity with respect to MS risk: obese MS participants with the allele occurred 16.2 times- and 13.8 times-more often than non-obese healthy participants in the EIMS and KPNC studies, respectively.

Although the study is limited by using self-reported BMIs at the age of 20 years and non-standarized methods of genotyping, the findings still have impact. Five years ago (2009-2010), 16.9% of children and adolescents in the United States were obese. This may translate into a growing population of people with MS in the future. Although there is no control over genes, there is control over BMI: perhaps a reduction in the number of obese adolescents will contribute to a reduction of the incidence of MS. However, this should be interpreted cautiously: there is only a correlation between obesity and MS, which does not mean causation.

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About Maureen Newman

Maureen Newman
Maureen Newman is a PhD student studying biomedical engineering at University of Rochester, working towards a career of research in biomaterials for drug delivery and regenerative medicine. She is an integral part of Dr. Danielle Benoit's laboratory, where she is investigating bone-homing therapeutics for osteoporosis treatment.
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