Evaluation of the role of MHC class II alleles, haplotypes and selected amino acid sequences in primary sclerosing XXXX .

@entity1 @entity1522 @entity1531 @entity3098 @entity991 @entity8167 @entity255 @entity1533
BACKGROUND AND AIMS: Genetic susceptibility to primary sclerosing @entity255 is associated with several different HLA haplotypes, though a single "shared" susceptibility allele has yet to be identified. Most recently, attention has focussed on the @entity1531 alleles in close proximity to the HLA class I, B locus. However, although there are strong associations with @entity1531 *008, implicating this or a closely linked allele as major risk factors, this explanation alone does not account for all of the MHC-encoded susceptibility and resistance to @entity991 . The present study re-examines HLA class II associations in a large single centre series of well-characterised @entity991 @entity1 . The specific aims of the study were to test existing associations and to develop hypotheses which together may account for all, or the majority, of the MHC-encoded susceptibility in @entity991 . METHODS: A total of 148 adult white northern European @entity1 and 134 control subjects were studied. HLA @entity1533 , @entity8167 , @entity3098 alleles and @entity1533 *04, @entity1533 *13 and DRB3 subtypes were determined by standard PCR-genotyping. RESULTS: The primary associations with the DRB3*0101-- @entity1533 *0301-- @entity8167 *0501-- @entity3098 *0201 and @entity1533 *1301-- @entity8167 *0103-- @entity3098 *0603 haplotypes were confirmed (O.R. = 2.69, p < 0.0000025 and O.R. = 3.8, p < 0.0005). In addition the strong protective influence of the @entity1533 *04-- @entity3098 *0302 haplotype was reaffirmed (O.R. = 0.26, p < 0.000025) and a previously unreported negative (i.e. protective) association with the @entity1533 *0701-- @entity3098 *0303 haplotype was also demonstrated (O.R. = 0.15, p < 0.005). Further analysis suggested that susceptibility/resistance encoded by the second and third susceptibility haplotypes and by the two resistance haplotypes may be determined by specific @entity1522 at DQbeta-87 and DQbeta-55, respectively.
