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Neurology. 2014 Mar 11;82(10):865-72. doi: 10.1212/WNL.0000000000000203. Epub 2014 Feb 5.

Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis.

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From the Institute of Environmental Medicine (A.K.H.), Neuroimmunology Unit, Department of Clinical Neuroscience (I.L.B., I.K.), and the Institute of Environmental Medicine (L.A.), Karolinska Institutet, Stockholm, Sweden; Genetic Epidemiology and Genomics Lab (L.B., M.G.), Division of Epidemiology, School of Public Health, University of California, Berkeley; Kaiser Permanente Division of Research (C.S.), Oakland, CA; Center for Molecular Medicine (I.K.) and Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine (T.O.), Karolinska Institutet at Karolinska University Hospital, Solna; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden.



We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS).


We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction.


In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5-35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1-46.8).


We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule-restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.

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