Mapping of the HLA-linked genes controlling the susceptibility to Takayasu’s arteritis

To further define the HLA-linked genes controlling the susceptibility to Takayasu’s arteritis, polymorphisms in five microsatellites around the HLA-B and MICA genes, C1-2-A, MIB, C1-4-1, C1-2-5, and C1-3-1, were investigated in 91 Japanese patients with Takayasu’s arteritis and 248 healthy Japanese controls. It was found that allele 238 of C1-2-A [60.4% in patients vs. 29.8% in controls, odds ratio (OR)=3.59, Pc<0.000004], allele 332 of MIB (22.0% vs. 6.1%, OR=4.32, Pc<0.0003), allele 208 of C1-2-5 (47.3% vs. 24.6%, OR=2.75, Pc=0.001), and allele 291 of C1-3-1 (62.6% vs. 44.8%, OR=2.07, Pc<0.02) were significantly associated with the disease. Combined analyses of polymorphisms in the HLA-B and MICA genes with those in the microsatellites suggest that there are two different disease-susceptible loci for Takayasu’s arteritis; one is mapped near the C1-2-A locus and the other is more closely linked to the HLA-B gene than to the MICA gene, because there are at least two different disease-associated HLA-B haplotypes, HLA-B*52 and -B*39.2 haplotypes, in which the disease-associated C1-2-A allele is shared in common.