title: MHC class I chain-related gene A transmembrane polymorphism modulates the extension of ulcerative colitis.
abstract: Recent evidence from several studies has suggested a genetic predisposition in the pathogenesis of ulcerative colitis (UC), which is especially related with major histocompatibility complex (MHC) genes. The aim of this study was to investigate the possible association of human leukocyte antigen (HLA-B, HLA-DR) and MHC class I chain-related-transmembrane (MICA-TM) polymorphism with the behavior and extension of UC. We selected 121 unrelated patients with UC. These were divided into two groups according to the extension of the disease: 31 patients with distal UC and 90 with wide extension UC; 116 blood donors were also selected as healthy controls, all of whom were typed for HLA-B, HLA-DR, and MICA-TM alleles. HLA-B7 was found to be overrepresented in distal UC patients compared with those with extensive UC (p(c) = 0.007, OR = 5.33) and healthy controls (p(c) = 0.03, OR = 4.09). The MICA-A5.1 allele was also increased in distal UC (p(c) = 0.015, OR = 3.82) when compared with extensive forms. These alleles are in strong linkage disequilibrium in our population. The MICA-A5 allele was significantly increased in extensive forms when compared with healthy controls(p(c) = 0.02, OR = 2.4). According to our results, MICA-A5.1 allele seems to be protective against extensive forms of UC, and MICA-A5 may condition a worse progression of the disease. These results are in agreement with other studies that suggest a similar role of such alleles in other diseases, such as insulin-dependent diabetes mellitus and celiac disease.
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Fdez-Morera
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Vázquez
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Rodero
authors.forename: Jesús
authors.initials: J
authors.lastname: Martínez-Borra
authors.forename: Pilar
authors.initials: P
authors.lastname: Niño
authors.forename: Segundo
authors.initials: S
authors.lastname: González
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
mesh_terms: D017668:Age of Onset; D000483:Alleles; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D013030:Spain
chemical_list: D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A