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Abstract
Background: Epstein-Barr virus infection, smoking, HLA-A*02, and DRB1*15 have all been proposed as risk factors for multiple sclerosis (MS). In 2010, Simon et al. described an interaction on the multiplicative scale between EBNA1 immunoglobulin G (IgG) and smoking regarding risk of MS, a finding that we attempted to replicate.
Methods: This Swedish case-control study consisted of patients with newly diagnosed MS and matched controls. Using logistic regression, we analyzed association to MS risk and interactions between EBNA1 IgG and smoking, HLA-DRB1*15, and A*02, respectively, on the multiplicative scale. In addition, we analyzed interactions on the additive scale using attributable proportion due to interaction (AP).
Results: We did not observe any interaction on the multiplicative scale between EBNA1 IgG and any of the 3 risk factors, smoking, DRB1*15, or absence of A*02, although in a conditional analysis the interaction with absence of A*02 becomes significant. However, we observed interactions on the additive scale between EBNA1 IgG and DRB1*15 (AP = 0.34, 95% confidence interval 0.11–0.57, p = 5 × 10−3) and between EBNA1 IgG and absence of A*02 (AP = 0.36, 0.13–0.59, p = 2 × 10−3) but not between smoking and DRB1*15 and EBNA1 IgG. The interaction between EBNA1 IgG and DRB1*15 was not significant in the conditional analysis.
Conclusion: We did not observe any interaction between EBNA1 IgG and smoking, regardless of scale used, and thus did not replicate the observations from Simon et al.
GLOSSARY
- AP=
- attributable proportion;
- CI=
- confidence interval;
- EBV=
- Epstein-Barr virus;
- EIMS=
- Epidemiologic Investigations in Multiple Sclerosis;
- HLA=
- human leukocyte antigen;
- IgG=
- immunoglobulin G;
- MS=
- multiple sclerosis;
- OR=
- odds ratio
Footnotes
Study funding: Supported by grants from the Swedish Association for Persons with Neurological Disabilities, The Swedish Research Council, The Söderbergs Foundation, the AFA Foundation, the Swedish Foundation for Working Life and Social Research, and the EU FP6 Integrated Project Neuropromise (LSHM-CT-2005–018637).
Editorial, page 1310
Supplemental data at www.neurology.org
- Received November 29, 2011.
- Accepted February 23, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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