K. Manabe et al., HUMAN-LEUKOCYTE ANTIGEN A1-B8-DR3-DQ2-DPB1-ASTERISK-0401 EXTENDED HAPLOTYPE IN AUTOIMMUNE HEPATITIS, Hepatology, 18(6), 1993, pp. 1334-1337
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.