title: Genetic markers linked to rheumatoid arthritis are also strongly associated with articular manifestations in ulcerative colitis patients.
abstract: Ulcerative colitis is often accompanied by the development of extraintestinal, mainly articular, manifestations. Genetic differences could be underlying that clinical heterogeneity. We performed a case-control study to determine whether TNFab microsatellites or HLA-DR alleles were associated with the development of articular manifestations in patients with ulcerative colitis. With that aim, a total of 84 ulcerative colitis patients with articular manifestations and 172 without them were genotyped for TNFab microsatellites and HLA-DR. A healthy control sample (n = 595) was also included for comparative purposes. Haplotypes were inferred with the Arlequin software. The influence of HLA-DRB1*0103 and HLA-B27, factors previously known to be associated with extraintestinal manifestations, was specifically addressed. We observed that TNFa6b5 minihaplotype increases the susceptibility to developing articular manifestations in ulcerative colitis patients (p = 0.003, OR = 2.39). The locus HLA-DR does not appear to be involved in these extraintestinal manifestations by itself; however, the frequency of subjects carrying TNFa6b5 in combination with DR1, DR7, or DR11 is very significantly increased in patients with articular manifestations (p = 3.9 x 10(-8)). The associations found were independent of DRB1*0103 and HLA-B27. Thus, it seems that the development of articular manifestations in ulcerative colitis patients appears to be influenced by some genetic factor(s) present in some major histocompatibility complex haplotypes.
authors.affiliation: Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. connunez@usc.es
authors.forename: Concepción
authors.initials: C
authors.lastname: Núñez
authors.forename: Diana Meda
authors.initials: DM
authors.lastname: Alecsandru
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Mendoza
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: Emilio Gómez
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martinez
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D017720:Molecular Epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha