However, using a sibling pair linkage analysis that restricts haplotype sharing probabilities to defined genetic models, we have not observed linkage of this region to susceptibility in MS. We discuss the basis for association and linkage and conclude that the DR15, DQ6, Dw2 haplotype does represent a susceptibility locus but its contribution to the pathogenesis is small; although it may interact epistatically with other susceptibility genes, this haplotype is not necessary for disease expression.
Among the candidate genes for multiple sclerosis (MS), the strongest influence is conferred by human leucocyte antigen (HLA) class II genes, in particular the DR2, DQ6, Dw2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602).
The other components of the commonest DR2-containing haplotype of this region, HLA-A3-B7-DR2-Dw2, also tend to be present at higher frequency in MS patients.
Linkage of a hypothesized multiple sclerosis susceptibility gene with certain haplotypes of HLA-A3, HLA-B7 HLA-DW2, and the new B group 4 can be inferred.
Normal or only slightly elevated frequencies of B7 and Dw2 were found in MS patients without oligoclonal CSF IgG (35 and 29%), normal CSF-IgG index (43 and 39%), and the most benign course (42 and 37%).