HLA class II alleles in Japanese patients with inflammatory bowel disease

Abstract

The association of various HLA class II loci with Crohn's disease (CD) and ulcerative colitis (UC) has yet to be fully elucidated. To determine whether there is an association of HLA class II genes (DR, DQ and DP alleles) with inflammatory bowel disease (IBD), HLA class II genes for polymorphisms were analyzed at the DNA level in 111 patients with CD, 81 with UC and 525 healthy controls by the polymerase chain reaction-sequence specific oligonucleotide probe method. Allele and haplotype frequencies were compared between these populations. Results were as follows: 1) the presence of DQB1*0402 (RR=3.90, Pc=0.0001) was positively associated with CD; 2) the presence of DRB1*1502 (RR=4.51, P<1X10(-8)), DRB5*0102 (RR=4.70, Pc<1x10(-8)), DQA1*0103 (RR=3.72, Pc=1x10(-5)), DQB1*06011 (RR=3.78, PC=1x10(-5)), DPA1*0201 (RR=3.23, Pc=0.0001) and DPB1*0901 (RR=4.83, PC<1x10(8)) was positively associated and that of DRB4*0101 (RR=0.20, Pc<1X10(-8)) and DQA1*0302 (RR=0.34, Pc=0.001) negatively associated with UC; 3) haplotype analysis showed a positive association between the presence of DRB1*0410-DQA1*0302-DQB1*0402 and DRB1*0802-DQA1*0401-DQB1*0402 with CD, and a negative association between the presence of DRB1*1502-DQA1*0103-DQB1*06011 and CD, there was no association of DRB1*08032-DQA1*0103-DQB1*06011 with CD; and 4) in UC, a positive association with the presence of DRB1*1502-DQA1*0103-DQB1*06011 was found, but DRB1*08032-DQA1*0103-DQB1*06011 was not associated with it. In conclusion, in CD in the Japanese population, HLA-linked disease susceptibility alleles appear to be DQB1*0402 and DRB1*1502, a disease resistance allele. In UC, DRB1*1502 appears to be a disease susceptibility allele.

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

“…In other serologic studies, the HLA class II DR1-DQ5 haplotype was found to be associated with CD in Caucasians [12,15,25]. Moreover, recent molecular analyses of the HLA class II genes in Japanese [16,23,24] and Caucasian populations [13,[26][27][28] (including the current study) demonstrated significant HLA class II allele and haplotype associations with IBD.…”

“…Two recent studies of Japanese CD patients, however, indicated a significant association with DQB1*0402 [16,23]. In those studies, DQB1*0402 was linked to DRB1*0410, which was also associated with CD.…”

“…Our previously reported association of DR2 with UC [19] was found here attributable only to DRB1*1502 (Table 3). In two recent studies from Japan, DRB1*1502 was associated with susceptibility as well as progression to UC [16,24]. Another study indicates that the DRB1*1501 allele confers protection from CD in Japanese [23].…”

“…In an English population study using DNA typing methods Satsangi et al found no association with DR2 in CD or UC patients [14]. However, three studies in Japanese populations using DNA typing methods indicated that DRB1*1501 showed a protective association with CD [23], and DRB1*1502 showed an association with UC [16,24]. In other serologic studies, the HLA class II DR1-DQ5 haplotype was found to be associated with CD in Caucasians [12,15,25].…”

“…The HLA class II genes, which have been associated with IBD in several studies [5][6][7][13][14][15][16], are plausible candidate genes because they play a fundamental role in peptide binding and T-cell receptor repertoire determination, and have been associated with various autoimmune and infectious diseases (reviewed in [17]). Finally, data from a number of experimental models of IBD indicate that HLA class II-restricted CD4 + T cells play a critical immunoregulatory role in IBD, and are essential to the regulation of intestinal immune responses [18].…”