Objectives: The aim of this study was to determine whether the tissue transglutaminase (tTG) gene is a causal factor in the pathogenesis of celiac disease (CD).
Methods: A total of 147 Dutch families with at least one patient with biopsy-proven CD were available for this study. In all patients, CD was diagnosed according to the revised European Society for Pediatric Gastroenterology and Nutrition criteria. A microsatellite marker in a noncoding region of the tTG gene was investigated for both linkage and association. Linkage was tested by determining the amount of allele sharing between affected brothers and sisters (affected sibling [sib] pair analysis). Association was determined by comparing transmission of certain tTG alleles from parents to CD patients to the nontransmitted alleles by the transmission/disequilibrium test.
Results: Linkage analysis did not show cosegregation of the tTG gene with celiac disease in our families, and there was no association between certain tTG alleles and celiac disease. Furthermore, the tTG gene could be excluded as a CD susceptibility gene.
Conclusion: Our results indicate that the tTG gene can be excluded as a major primary genetic factor in CD pathogenesis.