Major histocompatibility complex class II alleles and the course and outcome of MS: A population-based study

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.