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From the Department of Neurology (Drs. Weinshenker and Rodriguez), Department of Transfusion Medicine (Drs. Santrach and Moore), Section of Biostatistics, Department of Health Sciences Research (A.S. Bissonett, S.K. McDonnell, and Dr. Schaid), Mayo Clinic and Mayo Foundation, Rochester, MN.
Address correspondence and reprint requests to Dr. Brian G. Weinshenker, Department of Neurology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905.
Background: The major histocompatibility complex (MHC) has been consistently associated with susceptibility to MS and the course of several other human autoimmune diseases. A putative association between the course and severity of MS and the MHC remains controversial.
Methods: DR and DQ genotyping by either restriction fragment length polymorphism or sequence-specific PCR-based typing in 119 patients representing 73.4% of the population with MS evaluated in a cross-sectional disability survey and 100 healthy controls from Olmsted County, Minnesota.
Results: We found a positive association between MS susceptibility and the DR15-DQ6 and DR13-DQ7 haplotypes, and we found a negative association with the DR1-DQ5 haplotype. We found a trend to a positive association of primary progressive MS with DR4-DQ8 and DR1-DQ5 and an association of "bout onset" MS with DR17-DQ2. We did not find an association with disease severity, as defined by EDSS/duration.
Conclusion: Lack of consistency between different studies may be due to regional variation in MS and limitations of power but likely indicate a minor effect of MHC class II genes on the course and severity of MS.
Supported by grants from the Mayo Foundation. B.W. is supported by a grant from the National Multiple Sclerosis Society.
Presented in part at the 47th annual meeting of the American Academy of Neurology, Seattle, WA, May 1995.
Received December 3, 1997. Accepted in final form April 24, 1998.
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