42
Views
62
CrossRef citations to date
0
Altmetric
Research Article

Evaluation of the Role of MHC Class II Alleles, Haplotypes and Selected Amino Acid Sequences in Primary Sclerosing Cholangitis

&
Pages 555-564 | Published online: 07 Jul 2009
 

Abstract

Background and Aims: Genetic susceptibility to primary sclerosing cholangitis 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 MICA alleles in close proximity to the HLA class I, B locus. However, although there are strong associations with MICA*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 PSC. The present study re-examines HLA class II associations in a large single centre series of well-characterised PSC patients. 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 PSC. Methods: A total of 148 adult white northern European patients and 134 control subjects were studied. HLA DRB1, DQA1, DQB1 alleles and DRB1*04, DRB1*13 and DRB3 subtypes were determined by standard PCR-genotyping. Results: The primary associations with the DRB3*0101-DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*1301-DQA1*0103-DQB1*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 DRB1*04-DQB1*0302 haplotype was reaffirmed (O.R.=0.26, p <0.000025) and a previously unreported negative (i.e. protective) association with the DRB1*0701-DQB1*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 amino acids at DQ&#103 -87 and DQ&#103 -55, respectively.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.