An increased risk of Crohn's disease in individuals who inherit the HLA class II DRB3*0301 allele

David G. Forcione, Bruce Sands, Kurt J. Isselbacher, Anil Rustgi, Daniel K. Podolsky, Shiv Pillai

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The role of inflammatory T cells in Crohn's disease suggests that inherited variations in major histocompatibility complex (MHC) class II genes may be of pathogenetic importance in inflammatory bowel disease. The absence of consistent and strong associations with MHC class II genes in Caucasian patients with inflammatory bowel disease probably reflects the use of less precise typing approaches and the failure to type certain loci by any means. A PCR-sequence-specific oligonucleotide-based approach was used to type individual alleles of the HLA class II DRB1, DRB3, DRB4, and DRB5 loci in 40 patients with ulcerative colitis, 42 Crohn's disease patients, and 93 ethnically matched healthy controls. Detailed molecular typing of the above alleles has previously not been reported in patients with inflammatory bowel disease. A highly significant positive association with the HLA-DRB3*0301 allele was observed in patients with Crohn's disease (P = 0.0004) but not in patients with ulcerative colitis. The relative risk for this association was 7.04. Other less significant HLA class II associations were also noted in patients with Crohn's disease. One of these associations involved the HL4- DRB1*1302 allele, which is known to be in linkage disequilibrium with HLA- DRB3*0301. These data suggest that a single allele of an infrequently typed HLA class II locus is strongly associated with Crohn's disease and that MHC class II molecules may be important in its pathogenesis.

Original languageEnglish (US)
Pages (from-to)5094-5098
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number10
DOIs
StatePublished - May 14 1996

Keywords

  • HLA class II genotyping
  • disease susceptibility
  • inflammatory bowel disease
  • major histocompatibility complex

ASJC Scopus subject areas

  • General

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