MICA gene polymorphism in Takayasu's arteritis and Buerger's disease

To further clarify the HLA-linked genes susceptible to arterio-vasculitis o f unknown etiology, Takayasu's arteritis and Buerger's disease, polymorphis m in the MICA gene, a newly identified gene near the HLA-B gene and express ed in epithelial cell lineage, was investigated. Polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis and subsequent sequencin g of the MICA gene have revealed that there are 5 MICA alleles which are di fferent in the number of a GCT repeat in exon 5: MICA alleles MICA-1.1, -1. 2, -1.3 and -1.4 have 9, 6, 5 and 4 GCT repeats, respectively, and MICA-1.5 has 5 GCT repeats with a 1 bp frameshift insertion in the repeat. MICA gen otyping data in 81 Japanese patients with Takayasu's arteritis, 38 Japanese patients with Buerger's disease, and 160 healthy Japanese controls showed that MICA-1.2 and -1.4 were significantly associated with Takayasu's arteri tis and Buerger's disease, respectively. Because MICA-1.2 and -1.4 were in strong linkage disequilibria with HLA-B52 and -B54 in the Japanese populati ons, respectively, we have compared the odds ratio (OR) of the risk to the diseases for individuals having both or each of the disease-associated MICA and HLA-B alleles. It was found that MICA-1.2 gave a significantly high OR of risk to Takayasu's arteritis in the absence of HLA-B52, suggesting that the HLA-linked gene susceptible to Takayasu's arteritis is mapped near the MICA gene. In contrast, MICA-1.4 gave a significantly high OR of risk to B uerger's disease only in the presence of HLA-B54, suggesting that the HLA-l inked gene susceptible to Buerger's disease is linked to the HLA-B54-MICA-1 .4 haplotype, and may be differently mapped from that to Takayasu's arterit is. (C) 1998 Elsevier Science B.V. All rights reserved.