Coeliac disease and down syndrome: Associations not due to genetic linkage on chromosome 21

Background: Individuals with Down syndrome have an increased prevalence of coeliac disease (CD). The HLA region accounts for only 30% of the heritability of CD, and segregation analyses have suggested the involvement of at least one other non-HLA gene. Distribution of known HLA susceptibility types in Down syndrome and normal populations are similar and do not explain the difference in disease frequency. This study tests the hypothesis that the association between these disorders is due to a susceptibility gene for coeliac disease being present on chromosome 21. Methods: We studied 21 families multiply affected with CD, none of whom had Down syndrome. The typing information of six microsatellite markers across chromosome 21 was used to test linkage. Results: Negative results from lod score and model-free linkage analysis were obtained, providing no support for genetic linkage of coeliac disease to chromosome 21 in this population. Conclusions: The high prevalence of coeliac disease in Down syndrome is not due to an increased copy number of a polymorphic susceptibility gene on chromosome 21.