LINKAGE ANALYSIS OF HLA CLASS-II GENES IN SWEDISH MULTIPLEX FAMILIES WITH MULTIPLE-SCLEROSIS

We assessed the influence of human leukocyte antigen (HLA) class II as susceptibility genes in multiple sclerosis (MS) by linkage analysis. Other research groups, who have shown negative results in studies on a ffected sibling pairs, have questioned the influence of the HLA. class II genes, although they confirmed the association of the DR15,DQ6,Dw2 haplotype to MS. In this report, we find a significant lod score (>3) when using a 2-point linkage analysis of 49 small Swedish nuclear MS families with at least two affected family members, typed for HLA clas s II alleles by PCR amplification with sequence-specific primers. We o btained maximum lod scores when we used dominant or intermediate model s with low penetrance. We found that the positive effect on the total lod score was not confined to those families carrying the presumed sus ceptibility HLA-haplotype Dw2. This observation supports the notion of a functional role of the HLA class II molecules themselves in MS. In addition, we observed significant transmission distortion and an intra familial association of the MS-associated class II haplotype HLA-Dw2. These results indicate that the HLA class II genes are of clear import ance for MS in the studied population.