title: HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: a large-scale study.
abstract: Twin and family studies suggest there is a significant genetic component to primary biliary cirrhosis (PBC). However, the inability to replicate reported associations has been a recurring problem, with the only consistently reported genetic association that between PBC and HLA-DRB1*0801. However, recently even this has been questioned, and a number of novel associations have also been reported. We reinvestigated HLA class II DRB1, DQA1, and DQB1 alleles and haplotypes in a total of 492 well-characterized PBC patients, 412 from the United Kingdom and an additional 80 patients from northern Italy. There was a clear and significant association with HLA-DRB1*0801 in both groups of patients compared to population-specific healthy controls (12% versus 4% in the UK patients, P=.00087, OR=3.05; and 18% versus 6% in the Italian patients, P=.021, OR=3.15). There were also significant protective associations with DRB1*11 in the Italian patients (28% versus 47%, P=.0071, OR=0.42), but not in the UK patients (8% versus 8%) and a protective association with DRB1*13 in both series (14% versus 20%, P=.042, OR=0.65 in the UK patients; and 10% versus 31%, P=.00092, OR=0.25 in the Italian patients). In conclusion, a complex relationship exists between HLA and PBC, and some genetic associations may be population specific.
authors.affiliation: School of Clinical Medical Sciences (Hepatology), Faculty of Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, and Institute of Liver Studies, Kings College Hospital, London, UK. p.t.donaldson@ncl.ac.uk
authors.forename: Peter T
authors.initials: PT
authors.lastname: Donaldson
authors.forename: Anna
authors.initials: A
authors.lastname: Baragiotta
authors.forename: Michael A
authors.initials: MA
authors.lastname: Heneghan
authors.forename: Annarosa
authors.initials: A
authors.lastname: Floreani
authors.forename: Carla
authors.initials: C
authors.lastname: Venturi
authors.forename: James A
authors.initials: JA
authors.lastname: Underhill
authors.forename: David E J
authors.initials: DE
authors.lastname: Jones
authors.forename: Oliver F W
authors.initials: OF
authors.lastname: James
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Bassendine
mesh_terms: D000483:Alleles; D000596:Amino Acids / Q000378:metabolism*; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008105:Liver Cirrhosis, Biliary / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000596:Amino Acids; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D004247:DNA