ANALYSIS OF HLA-CLASS-II-ENCODED ANTIGEN-PROCESSING GENES TAP1 AND TAP2 IN PRIMARY BILIARY-CIRRHOSIS

The search for genes involved in the aetiology of primary biliary cirr hosis (PBC) has centred on the major histocompatibility complex (MHC) on chromosome 6. Genotyping studies have confirmed an association with HLA class II allele DR8. We investigated polymorphisms in two newly i dentified genes (TAP1 and TAP2) situated close to the DR locus and tho ught to encode membrane transporter molecules involved in endogenous a ntigen processing. Genomic DNA extracted from PBC patients was compare d with local healthy controls. TAP1 was analysed by amplification refr actory mutation system (ARMS) PCR, and two alleles (A and B) were iden tified. In 126 PBC patients and 116 controls, allele frequencies were (A:B) 81:19% and 79:21%, respectively (NS). TAP2 analysis was by PCR f ol-lowed by BfaI restriction digest, and again two alleles (A and B) w ere identified. Their frequencies in 109 PBC patients and 96 controls were (A:B) 76:24% and 73:27%, respectively (NS). No TAP1-TAP2 haplotyp e was associated with PBC. TAP allele frequencies were estimated withi n the DR8 subgroups (22 PBC, 14 controls). B allele frequency for TAP1 was increased in both DR8-positive PBC patients and controls compared with DR8-negative patients and controls (41% vs. 14% in PBC; 43% vs. 18% in controls), but no disease association was found. However, the i ncreased frequency of TAP1B in DR8-positive subjects (42% DR8-positive vs. 16% DR8-negative, p < 0.001) indicates linkage disequilibrium bet ween these two loci.