HUMAN-LEUKOCYTE ANTIGEN A1-B8-DR3-DQ2-DPB1-ASTERISK-0401 EXTENDED HAPLOTYPE IN AUTOIMMUNE HEPATITIS

Genetic susceptibility to autoimmune hepatitis is associated with the human leukocyte antigen haplotype A1-B8-DR3 and DR4. To date, only one study in Japan has considered the human leukocyte antigen DP locus in this disease, and no studies have been reported in whites. In this st udy we used a series of sequence-specific oligonucleotide probes to de termine human leukocyte antigen DPB1 genotypes in 101 unrelated white northern European patients and 105 racially and geographically matched controls. The aims of the study were twofold: first, to determine the degree of DPB-encoded susceptibility to autoimmune hepatitis, and, se cond, to establish whether susceptibility can be extended to include h uman leukocyte antigen DPB. None of 17 DPB1 alleles was significantly associated with the susceptibility to autoimmune hepatitis. Although o ne particular seven-locus haplotype -DRB30101-DRB1*0301-DQA1*0501-DQB 10201-DPB1*0401 was significantly associated with the disease (27% vs . 7%, relative risk = 5.14, p < 0.0005), the association with this hap lotype was weaker than that for the six-locus haplotype excluding DPB (40% vs. 11%, RR = 5.52, p < 0.0005). When the patients first seen at ages younger than 16 yr (pediatric patients) were considered separatel y, the greatest relative risk was for the seven-locus haplotype (41% v s. 7%; relative risk = 9.60, p < 0.0005). The results of this study fu rther confirm that major histocompatibility complex-encoded susceptibi lity to autoimmune hepatitis is located at or close to the human leuko cyte antigen DR locus; however, the Al-B8-DR3-DQ2-DPB10401 extended h aplotype may be important in determining the age of onset and severity of disease.