Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis.

Abstract

OBJECTIVES:

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%).

CONCLUSION:

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: Ritva M Koskela, Tuomo J Karttunen, Seppo E Niemelä, Juhani K Lehtola, Jorma Ilonen, Riitta A Karttunen
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 20 Issue 4 Pg. 276-82 (Apr 2008) ISSN: 0954-691X [Print] England
• PMID: 18334870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Genetic Markers
• HLA-DQ Antigens
• HLA-DQ2 antigen
• HLA-DR3 Antigen
• Tumor Necrosis Factor-alpha

Topics

• Celiac Disease (diagnosis, epidemiology, genetics)
• Colitis, Microscopic (epidemiology, genetics)
• Female
• Finland (epidemiology)
• Genetic Markers
• Genetic Predisposition to Disease (epidemiology, genetics)
• HLA-DQ Antigens (genetics)
• HLA-DR3 Antigen (genetics)
• Humans
• Male
• Polymorphism, Genetic (genetics)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (genetics)