Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet disease.
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 Behcet 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 Behcet disease with MICA rather than HLA-B.
Mizuki
N
N
Department of Ophthalmology, Yokohama City University School of Medicine, Kanazawa-ku, Kanagawa, Japan.
Ota
M
M
Kimura
M
M
Ohno
S
S
Ando
H
H
Katsuyama
Y
Y
Yamazaki
M
M
Watanabe
K
K
Goto
K
K
Nakamura
S
S
Bahram
S
S
Inoko
H
H
D044466:Asian People; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001528:Behcet Syndrome / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D016009:Chi-Square Distribution; D018244:Chromosomes, Artificial, Yeast; D002896:Chromosomes, Human, Pair 6; D003360:Cosmids; D005091:Exons / Q000235:genetics; D005260:Female; D015235:HLA-B Antigens / Q000235:genetics; D059949:HLA-B51 Antigen; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D010641:Phenotype; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D018911:Trinucleotide Repeats / Q000235:genetics*
D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D008565:Membrane Proteins