HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: A large-scale study
✍ Scribed by Peter T. Donaldson; Anna Baragiotta; Michael A. Heneghan; Annarosa Floreani; Carla Venturi; James A. Underhill; David E.J. Jones; Oliver F.W. James; Margaret F. Bassendine
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 177 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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.