Amino Acid Polymorphism at Residue 71 in HLA-DR Beta Chain Plays a Critical Role in Susceptibility to Ulcerative Colitis

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Abstract
The association of ulcerative colitis withdistinct HLA-DRB1 alleles has not been easy toascertain. Recent studies show that among HLA-DR2alleles, DRB1*15 but not DRB1*16, is associated with thedisease. Similarly, in the HLA-DR1 group, only DRB1*0103is increased in ulcerative colitis patients. The aim ofour study was to identify critical DRB1 residues thatmight account for these differences. We typed 121 patients with ulcerative colitis and 275controls using gene amplification and sequence-specificoligonucleotide probing for HLA-DRB1 and DRB3. Weobserved a strong negative association between HLA-DRB1 alleles that encode lysine at position 71 intheir β-chain and susceptibility to ulcerativecolitis. Differences in the prevalence among otheralleles differing only in the third hypervariable region suggested a hierarchy of susceptible andprotective class II alleles related to the presence ofan acidic, neutral, or basic amino acid residue atposition 71. These data implicate most strongly theamino acid residues in the third hypervariable regionof the DRβ chain, especially DRβ71, in theassociation between ulcerative colitis and HLA. However,this does not exclude the contribution of other parts of the molecule and otherimmunoregulatory genes.