No polymorphism in the tissue transglutaminase gene detected in coeliac disease patients

Background: The autoantigen for the anti-endomysial antibody (AEA) found in coeliac disease has recently been reported to be the enzyme tissue transgl utaminase (tTG). Polymorphisms in the gene for tTG would result in differen t enzymic isoforms being expressed. Certain isoforms may interact with glia din to create antigenic neoepitopes, which could then generate an immune re sponse in genetically predisposed individuals possessing major histocompati bility complex (MHC) class II DQ2. Methods: We have sequenced the coding region of tTG in coeliac patients and normal controls. Total RNA was extracted from mucosal biopsies from eight AEA-positive histologically proven coeliac disease patients and four contro l patients with a histologically normal duodenum and a negative AEA. The 2- kb coding region of tTG was amplified in overlapping fragments by reverse t ranscription polymerase chain reaction (PCR), using five sets of PCR primer s. Each overlapping PCR fragment was sequenced using the fmol DNA sequencin g system. Results: tTG transcripts were detected in all samples. There was no differe nce in the coding sequence of tTG between the four control and eight coelia c patients, even though we observed differences in sequence between our stu dy and the original published sequence. These differences have also been re ported in sequences published subsequent to the original description. Conclusions: Polymorphisms in the tTG gene have not been observed in coelia c disease patients and therefore cannot explain the creation of neoepitopes .