MICA gene polymorphism in Takayasuʹs arteritis and Buergerʹs disease

To further clarify the HLA-linked genes susceptible to arterio-vasculitis of unknown etiology, Takayasuʹs arteritis and Buergerʹs disease, polymorphism in the MICA gene, a newly identified gene near the HLA-B gene and expressed in epithelial cell lineage, was investigated. Polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis and subsequent sequencing of the MICA gene have revealed that there are 5 MICA alleles which are different 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 genotyping data in 81 Japanese patients with Takayasuʹs arteritis, 38 Japanese patients with Buergerʹs disease, and 160 healthy Japanese controls showed that MICA-1.2 and -1.4 were significantly associated with Takayasuʹs arteritis and Buergerʹs disease, respectively. Because MICA-1.2 and -1.4 were in strong linkage disequilibria with HLA-B52 and -B54 in the Japanese populations, 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 Takayasuʹs arteritis in the absence of HLA-B52, suggesting that the HLA-linked gene susceptible to Takayasuʹs arteritis is mapped near the MICA gene. In contrast, MICA-1.4 gave a significantly high OR of risk to Buergerʹs disease only in the presence of HLA-B54, suggesting that the HLA-linked gene susceptible to Buergerʹs disease is linked to the HLA-B54-MICA-1.4 haplotype, and may be differently mapped from that to Takayasuʹs arteritis.