A close relationship of triplet repeat polymorphism in MHC class I chain-related gene A (MICA) to the disease susceptibility and behavior in ulcerative colitis

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) has been found near the HLA-B gene. The MICA molecule is exclusively expres sed on gastrointestinal epithelium and recognized by intestinal epithelial gamma delta T cells, where it exhibits a triplet repeat polymorphism in the transmembrane region. We investigated the possible correlation between MIC A genetic polymorphism and ulcerative colitis (UC). Eighty three patients w ith UC and 132 unrelated controls were included in this study. All subjects were Japanese. A triplet repeat polymorphism in the transmembrane region o f the MICA was determined by direct sequencing procedures after amplificati on by a polymerase chain reaction. A significantly higher allele and phenot ype frequencies of MICA A6 allele were observed in patients with UC than co ntrols (allele frequency: P-c=0.000011, phenotype frequency: P-c=0.0049 add s ratio=2.62). A6 homozygous patients with UC showed significantly earlier onset of UC than patients without the A6 allele (P-c=0.0042). Phenotypes of MICA A6 allele in Japanese are closely related to the disease susceptibili ty and behavior in UC. Examinations of MICA polymorphism in other ethnic gr oups may provide important information about the locus of primary responsib le gene for UC.