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

Abstract

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) has been found near the HLA-B gene. The MICA molecule is exclusively expressed 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 MICA genetic polymorphism and ulcerative colitis (UC). Eighty-three patients with UC and 132 unrelated controls were included in this study. All subjects were Japanese. A triplet repeat polymorphism in the transmembrane region of the MICA was determined by direct sequencing procedures after amplification by a polymerase chain reaction. A significantly higher allele and phenotype frequencies of MICA A6 allele were observed in patients with UC than controls (allele frequency: P(c)=0.000011, phenotype frequency: P(c)=0.0049 odds 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 susceptibility and behavior in UC. Examinations of MICA polymorphism in other ethnic groups may provide important information about the locus of primary responsible gene for UC.

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

“…Investigations into the possible influence of MIC polymorphism in celiac disease, a gluten-sensitive enteropathy, suggest a causal role, [16][17][18] although similar studies of IBD have produced conflicting results. [19][20][21][22] In contrast to the MIC genes, NKG2D displays limited polymorphism 23 and has not previously been investigated in susceptibility to UC.…”

The increase of MICA gene A9 allele associated with gastric cancer and less schirrous change

“…The alleles vary among individuals, and hence polymorphism of MICA can be used for genetic mapping and analyses of disease susceptibility. For example, increased frequency of MICA A6 allele was found in patients with oral squamous cell carcinoma (Liu et al, 2002), Behcet's disease (Molinotti et al, 2001), and ulcerative colitis (Sugimura et al, 2001). In addition, increased frequency of A9 allele was reported in psoriatic arthritis (Gonzalez et al, 2001) and type I diabetes (Lee et al, 2000).…”

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset

“…Certain MICA-STR alleles have been associated with immune-mediated diseases [12,[25][26][27][28][29][30], including IBD: some revealed an association of MICA*A6 [31,32] or MICA*A5.1 with UC [33,34], while these results could not be replicated in other cohorts [35][36][37]. Moreover, MICA-STR alleles have been associated with UC phenotype, as location of disease [32,38], age at onset [32,39] or extraintestinal manifestations (EIMs) [7,33,39].…”

“…MICA*A6 was also in LD with others alleles HLA-B, but these haplotypes were not associated with disease. B*52 and B*52/MICA*A6 UC association has already been described [31,32].…”

“…Moreover, MICA-STR alleles have been associated with UC phenotype, as location of disease [32,38], age at onset [32,39] or extraintestinal manifestations (EIMs) [7,33,39]. Kamoun et al [39] suggested the association of MICA with CD, but in many studies there was no evidence of this association [7,[35][36][37].…”