DNA polymorphism of HLA class II genes in primary biliary cirrhosis

Abstract

We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary biliary cirrhosis (PBC) and in healthy Danes. The following genetic markers were found with increased frequencies in PBC: HLA-B8 (relative risk, RR = 2.4, P less than 0.05, 'corrected' P greater than 0.05), HLA-DR3 (RR = 3.4, P less than 0.01, 'corrected' P less than 0.05), the DRB3*01/02/03 (DRw52) associated DRB Bgl II 9.1 kilobase (kb) fragment (RR = 2.9; P less than 0.05, 'corrected' P greater than 0.05), the DQA1*0501 associated DQA Taq I 4.8 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05), the DQB1*0201 (DQw2) associated DQB Hin dIII 11.5 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05). No DNA fragments specific for DRB1*0301 (DR3) could be identified. The frequencies in PBC of other genetic markers including DRw8, DRB1*08, HLA-DP antigens, DPA, and DPB genes did not differ significantly from those in controls. The associations between PBC and B8, DR3, DQA1*0501, and DQB1*0201, which are frequently found together on the same haplotype, are at variance with recent reports on associations between PBC and Drw8. The discrepancy suggests that PBC is genetically heterogenous.

Human leukocyte antigen associations in Finnish liver transplantations due to primary sclerosing cholangitis and primary biliary cirrhosis

“…A similar association between HLA-DR3 and PBC was found in a Danish study [20] which, however, did not find any increase in HLA-DR8 in their study population. Furthermore, HLA-A28 was weakly positively and HLA-DR5 was weakly negatively associated with PBC in the present study.…”

“…Previous studies have reported an increased frequency of HLA-DR8 [16][17][18][19][20][21][22] and HLA-DR3 [20,23] in PBC patients compared to referent persons. In one study [16], HLA-DR5 had decreased frequency in PBC as compared to referent persons, and in another study [22], HLA DRB1*1302 (DR6) and HLA DRB1*1501 (DR2) were found to be negatively associated with PBC.…”

Genes and (auto)immunity in primary biliary cirrhosis

“…36 It is possible that positive association might be 41 This association was not confirmed in several other studies from different non-British European populations. 32,35,36,42,43 Moreover, other European studies suggested significant associations of PBC with DR3 29,35 and DPB1*0301, 44 while the most recent study from the United States demonstrated an association between DRB1*08-DQA1*0401-DQB1*04 haplotype and PBC, albeit in a minority of patients. 40 Finally, studies from Japan failed to provide a consistent picture of HLA class II associations with PBC.…”

“…In the past, studies performed on small series of subjects (between 21 and 75) have examined the association between HLA class I molecules and PBC susceptibility, [29][30][31][32][33][34][35] but the conclusions of such earlier reports were affected by several major flaws. First, the small patient populations evaluated in these studies may account for a limited statistical power of comparisons.…”

Genetics and Genomics of Primary Biliary Cirrhosis

“…A limited amount of effort has been placed on assessing the potential association of HLA class I alleles with PBC, with a handful of small studies finding no associations (34)(35)(36)38,45,46,48). More recently, a few rare HLA-B alleles were found to be associated with PBC in an Italian study of 112 PBC patients and 558 controls (53).…”