Open AccessA population‐ and family‐based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease
Author(s) -
Silverberg Mark S.,
Mirea Lucia,
Bull Shelley B.,
Murphy Janet E.,
Steinhart A. Hillary,
Greenberg Gordon R.,
McLeod Robin S.,
Cohen Zane,
Wade Judith A.,
Siminovitch Katherine A.
Publication year - 2003
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1097/00054725-200301000-00001
Subject(s) - inflammatory bowel disease , ulcerative colitis , medicine , population , immunology , allele , human leukocyte antigen , disease , gastroenterology , genetics , biology , antigen , environmental health , gene
The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population‐ and family‐based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB1*0103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case–control analysis of non‐Jewish IBD‐affected individuals. This association was apparent among both Crohn's disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non‐Jewish IBD population by results of family‐based association analysis using the transmission disequilibrium test. HLA DQB1*0501 was also associated with IBD (OR = 1.64, p = 0.02) in the non‐Jewish population, but statistically significant association of this allele with disease was not detected for Crohn's disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non‐Jewish IBD families, IBD was as strongly associated with the DRB1*0103 DQB1*0501 haplotype as with the DRB1*0103 allele alone. The carrier frequency of the DRB1*0103 allele was found to be 10‐fold higher in Crohn's disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB1*0103 allele with both Crohn's disease and ulcerative colitis and with large intestine–restricted disease in non‐Jewish IBD patients and therefore identify HLA DRB1*0103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.