Amino acid polymorphism at residue 71 in HLA-DR beta chain plays a critical role in susceptibility to ulcerative colitis

The association of ulcerative colitis with distinct HLA-DRB1 alleles has no t been easy to ascertain. Recent studies show that among HLA-DR2 alleles, D RB1*15 but not DRB1*16, is associated with the disease. Similarly, in the H LA-DR1 group, only DRB1*0103 is increased in ulcerative colitis patients. T he aim of our study was to identify critical DRB1 residues that might accou nt for these differences. We typed 121 patients with ulcerative colitis and 275 controls using gene amplification and sequence-specific oligonucleotid e probing for HLA-DRB1 and DRB3. We observed a strong negative association between HLA-DRB1 alleles that encode lysine at position 71 in their beta-ch ain and susceptibility to ulcerative colitis. Differences in the prevalence among other alleles differing only in the third hypervariable region sugge sted a hierarchy of susceptible and protective class II alleles related to the presence of an acidic, neutral, or basic amino acid residue at position 71. These data implicate most strongly the amino acid residues in the thir d hypervariable region of the DR beta chain, especially DR beta 71, in the association between ulcerative colitis and HLA. However, this does not excl ude the contribution of other Darts of the molecule and other immunoregulat ory genes.