Abstract
Objective: 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).
Methods: 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.
Results: 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).
Conclusions: 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.
GLOSSARY
- AP=
- attributable proportion due to interaction;
- BMI=
- body mass index;
- CI=
- confidence interval;
- EAE=
- experimental autoimmune encephalomyelitis;
- EIMS=
- Epidemiological Investigation of MS;
- HLA=
- human leukocyte antigen;
- KPNC=
- Kaiser Permanente Medical Care Plan, Northern California Region;
- MS=
- multiple sclerosis;
- OR=
- odds ratio;
- SNP=
- single nucleotide polymorphism
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 826
Supplemental data at Neurology.org
- Received June 14, 2013.
- Accepted in final form November 1, 2013.
- © 2014 American Academy of Neurology
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