HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients

Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis

“…We already reported that a predisposition to type 1 AIH in Japanese was associated with the HLA-B54/ DRB1*0405/ DQB1*0401 haplotype [11]. In Japanese, DQB1*0401 is in very strong linkage disequilibrium with DRB1*0405 and only one patient with the DRB1*0405 allele did not have the DQB1*0401 allele.…”

“…In our earlier study, we proposed that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (arginine on DR2 and histidine on DR4), contributes to the susceptibility to type 1 AIH among Japanese, since all of the 6 DR4-negative patients with AIH (n=53) had DR2 [11]. However, our current study revealed that 10 out of the 77 AIH patients were negative for both DR4 and DR15 (DR2), and 32.5% of AIH patients and 39.1% of controls had DR15 (DRB1*1501; OR 0.44, DRB1*1502; OR 1.03).…”

“…Seventy seven patients with type 1 AIH and 248 healthy Japanese controls were enrolled for investigation of genetic association with polymorphic genetic markers around the HLA region. Forty-six of these 77 patients were included in our earlier study [11]. They were all residents of Nagano Prefecture, Japan, and their racial backgrounds were all Japanese.…”

“…Several studies from ethnically different countries have clarified strong genetic bases for both disease susceptibility and behavior [4][5][6][7][8][9][10][11][12][13][14]. Recently, molecular analysis by the use of PCR-based DNA typing techniques have shown that the susceptibility to develop type 1 AIH is associated specifically with the DRB1*0301 and DRB1*0401 alleles in Caucasians [6][7][8][9][10], the DRB1*0405 allele in Japanese [11] and Argentine adults [12], DRB1*0404 in Mexicans [13], and DRB1*1301 in Argentine children [12] and Brazilians [14] at the HLA class II DRB1 locus, which encodes a polymorphic β chain of the HLA-DR antigen.…”

Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

“…17,18 In Japan where HLA DR3 is uncommon, patients with autoimmune hepatitis typically have HLA DR4, and they tend to be elderly with mild disease and excellent treatment outcomes. 19,20 The HLA pheno-types of different age groups with autoimmune hepatitis in North America have not been fully defined. HLA distinctions between the young and old in this geographic region may not only affect clinical features and outcome but generate hypotheses about etiologic mechanisms.…”