HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis. 
The human leukocyte antigen (HLA) region has been implicated in the disease susceptibility of inflammatory bowel disease by several linkage and association studies.  In Caucasians, HLA-DRB1 has been reported to determine the clinical phenotypes of ulcerative colitis (UC).  Others and we previously reported that HLA-DRB1*1502 was strongly associated with UC in the Japanese population.  However, the contribution of HLA-DRB1 to the clinical phenotypes in Japanese UC has not been elucidated yet.  The aim of this study was to determine whether HLA-DRB1 alleles were associated with the clinical phenotypes in Japanese patients with UC.  A total of 353 patients with UC were recruited.  Patients were classified into subgroups by sex, age at diagnosis, disease extent, need for steroid therapy or need for surgical treatment.  The allele frequency of HLA-DRB1*08 was significantly higher in patients whose disease extended beyond the rectum (left-sided and extensive UC) than in those with proctitis [odds ratio (OR)=2.20, Pc=0.043).  The allele frequency of HLA-DRB1*09 was significantly higher in patients with UC diagnosed at the age of 40 years or older than in those with UC diagnosed before the age of 40 years (OR=2.31, Pc=0.022).  Besides these positive associations, no significant differences were found in the allele frequencies between the other subgroups.  We conclude that HLA-DRB1*09 is associated with the age at diagnosis and HLA-DRB1*08 is associated with the disease extent of UC in Japanese.  These results indicate that HLA-DRB1 is not only associated with the overall UC susceptibility but also associated with the clinical phenotypes in Japanese.