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

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD) are the clinical entities comprising idiopathic inflammatory bowel disease (IBD). Previous studies on the association of IBD and human leukocyte antigen (HLA) class II genes suggested a role for HLA in this disease. Here we present HLA class II (DRB1, DQB1, DQA1, DPB1) allele and haplotype distributions determined using the polymerase chain reaction and sequence-specific oligonucleotide probe methods. A total of 578 UC and CD Caucasian patients and controls from Jewish (Ashkenazi) and non-Jewish populations was examined. Our previously reported association of DR1-DQ5 with CD was attributable to DRB1*0103. A dramatic association with IBD and the highly unusual DRB1*0103-DQA1*0501-DQB1*0301 haplotype (OR = 6.6, p = 0.036) was found. The more common DR1 haplotype, DRB1*0103-DQA1*0101-DQB1*0501, was also associated with IBD (OR = 3.1, p = 0.014), a result suggesting that interaction between DR and DQ may determine the extent of disease risk. Our previously reported association of DR2 with UC was attributable to DRB1*1502 (OR = 2.6, p = 0.006). At the DPB1 locus, a significant association of DPB1*0401 with CD was observed for the combined populations (OR = 1.85, p = 0.007). These observations indicate that some class II alleles and haplotypes confer susceptibility to both UC and CD, implying common immunogenetic mechanisms of pathogenesis, while others confer risk to only one of these diseases, and illustrate the value of DNA HLA typing in disease susceptibility analyses.

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

“…The up-regulation of antigen presentation genes is consistent with increased expression of HLA Class II molecules that typically occurs in IBD in humans [29]. HLA Class II genes have been associated with risk of IBD in a number of populations [30,31] (reviewed in ref. [32]).…”

Sex stratification of an inflammatory bowel disease genome search shows male-specific linkage to the HLA region of chromosome 6

“…Several studies have demonstrated an association between HLA class II alleles and susceptibility to both CD and UC. 27,28 The TNFa locus is a functional and positional candidate gene for IBD, but association studies involving TNFa polymorphisms and IBD have given inconsistent results.…”

Inflammatory bowel disease: Genetic and epidemiologic considerations

“…Replicated HLA class Ⅱ associations in IBD include HLA-DRB1*1502 (serological marker HLA-DR2) [76] association with UC, and HLA-DRB1*0103 association with UC and colonic CD [77,78] . HLA-DRB1*0103 is noteworthy in that it is a risk factor for both UC and colonic CD, suggesting it may play a role in chronic inflammation of the colon independent of major IBD phenotype (i.e., CD or UC) [78] .…”