title: Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis.
abstract: OBJECTIVE
  Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied.
  
  
  METHODS
  Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study.
  
  
  RESULTS
  HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%).
  
  
  CONCLUSIONS
  Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.
authors.affiliation: Department of Internal Medicine, Kanta-Häme Central Hospital, University of Oulu, Oulu, Finland. ritva.koskela@oulu.fi
authors.forename: Ritva M
authors.initials: RM
authors.lastname: Koskela
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
authors.forename: Seppo E
authors.initials: SE
authors.lastname: Niemelä
authors.forename: Juhani K
authors.initials: JK
authors.lastname: Lehtola
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Riitta A
authors.initials: RA
authors.lastname: Karttunen
mesh_terms: D002446:Celiac Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D046728:Colitis, Microscopic / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha