Stratification analysis of MICA triplet repeat polymorphisms and HLA antigens associated with ulcerative colitis in Japanese

We previously reported a conserved haplotype of HLA B52-DR2 and a significa ntly high frequency of the major histocompatibility complex (MHC) class I c hain-related gene A (MICA) transmembrane-short tandem repeat (TM-STR) 6 all ele in Japanese patients with ulcerative colitis (UC). To examine the predo minance of the MICA TM-STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC w as estimated following stratification of the patients to control for any po ssible confounding effects of other alleles positively associated with UC. Sixty-four patients with UC and 236 unrelated healthy controls were include d in this study. All subjects were Japanese. BLA-A, -B, -C, and -DR antigen s were determined serologically. A triplet repeat polymorphism of the YWCA was determined by direct sequencing. To control for the effect of linkage d isequilibrium, Mantel-Haenszel weighed odds ratios were calculated. Signifi cantly higher phenotype frequencies of B52, WCA TM-STR 6, and DR2 were obse rved in patients with UC. Linkage disequilibria. among alleles associated w ith UC revealed that a B52 - MICA TM-STR 6 - DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA-1352 was est imated after patient stratification for the possible confounding effect of MICA TM-STR 6 or DR2, a strong significant association of B52 with UC was s till observed. In contrast, no association with UC was observed for MICA TM -STR 6 or DR2, after stratification of the possible confounding effect of H LA-1352. These results imply that the significant increase in MICA TM-STR 6 in Japanese patients with UC is attributable to linkage disequilibrium wit h HLA-1352.