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

Clin Exp Immunol. 2016 Jun;184(3):323-31. doi: 10.1111/cei.12786. Epub 2016 Apr 5.

Abstract

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.

Keywords: MHC; autoimmunity; cell surface molecules; inflammation; molecular biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscess / diagnosis
  • Abscess / genetics
  • Abscess / immunology*
  • Abscess / pathology
  • Adult
  • Age of Onset
  • Alleles
  • Amino Acid Sequence
  • Case-Control Studies
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / pathology
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / immunology
  • HLA-B52 Antigen / genetics
  • HLA-B52 Antigen / immunology
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Male
  • Middle Aged
  • Models, Molecular
  • Odds Ratio
  • Polymorphism, Genetic / immunology*
  • Protein Domains
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Sequence Alignment

Substances

  • HLA-B27 Antigen
  • HLA-B52 Antigen
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • Protein Isoforms