Triplet repeat polymorphism in the transmembrane region of the MICA gene: A strong association of six GCT repetitions with Behçet disease

• DOI: 10.1073/pnas.94.4.1298
• Publication Date: 2002-07-26T14:31:39Z
• Authors: Nobuhisa Mizuki; Masao Ota; Minoru Kimura; Shigeaki Ohno; Hitoshi Ando; Yoshihiko Katsuyama; Masaaki Yamazaki; Koji Watanabe; Kaori Goto; Satoshi Nakamura; Seiamak Bahram; Hidetoshi Inoko
• Keywords: Male; B-Lymphocytes; Chi-Square Distribution; Base Sequence; Behcet Syndrome; Histocompatibility Antigens Class I; Molecular Sequence Data; Membrane Proteins; Exons; Cosmids; Cell Line; 3. Good health; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Asian People; Japan; HLA-B Antigens; HLA-B51 Antigen; Humans; Chromosomes, Human, Pair 6; Female; Chromosomes, Artificial, Yeast

A member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), MICA, has been recently identified near the HLA-B gene on the short arm of human chromosome 6. The predicted amino acid sequence of the MICA chain suggests that it folds similarly to typical class I chains and may have the capacity to bind peptides or other short ligands. Therefore, MICA is predicted to have a specialized function in antigen presentation or T cell recognition. During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT/AGC) n in the transmembrane (TM) region of the MICA gene. In 68 HLA homozygous B cell lines, 5 distinct alleles of this microsatellite sequence were detected. One of them contained an additional one base insertion that created a frameshift mutation resulting in a premature termination codon in the TM region. This particular allele may encode a soluble, secreted form of the MICA molecule. In addition, we have investigated this microsatellite polymorphism in 77 Japanese patients with Behçet disease, which is known to be associated with HLA-B51. The microsatellite allele consisting of 6 repetitions of GCT/AGC was present at significantly higher frequency in the patient group ( Pc = 0.00055) than in a control population. Furthermore, the (GCT/AGC) 6 allele was present in all B51 positive patients and in an additional 13 B51 negative patients. These results suggest the possibility of a primary association of Behçet disease with MICA rather than HLA-B.