title: MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.
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.
authors.affiliation: Section of Immunology, Hospital Virgen de las Nieves.|University of Granada.
authors.forename: A
authors.initials: A
authors.lastname: Martinez-Chamorro
authors.affiliation: Section of Immunology, Hospital Virgen de las Nieves.
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Digestive Section, Hospital Virgen de las Nieves.
authors.forename: M
authors.initials: M
authors.lastname: Gómez-García
authors.affiliation: Digestive Section, Hospital Virgen de las Nieves.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cabello
authors.affiliation: Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.affiliation: Section of Immunology, Hospital Virgen de las Nieves.|University of Granada.
authors.forename: M Á
authors.initials: MÁ
authors.lastname: Lopez-Nevot
mesh_terms: D000038:Abscess / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology; D059950:HLA-B52 Antigen / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000276:immunology*; D000072417:Protein Domains; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment
chemical_list: D015796:HLA-B27 Antigen; D059950:HLA-B52 Antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D020033:Protein Isoforms
keywords: MHC; autoimmunity; cell surface molecules; inflammation; molecular biology