Linkage disequilibrium between intra-locus variants in the aminopeptidase n gene and test of their association with coeliac disease

Coeliac disease (CD) is a multigenic and multifactorial enteropathy trigger ed by gluten-composing proteins. A possible involvement of the intestinal A minopeptidase N (APN) was investigated by an association analysis. SSCP ana lysis detected four variants at position 281, 378, 958 and 2957 (referred t o no. g178535, GenBank) that were studied in 193 Italian CD families. The h aplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D' = D/D-max) between the polymorphic sites were ca lculated. Significant D' values ranged between 0.78 and 0.31. Association w ith CD was tested by TDT (Transmission Disequilibrium Test) utilizing as ma rkers the nucleotide substitutions and their haplotypic combinations. No st atistically significant transmission distortion to the probands or to their clinically silent sibs was observed. Our data exclude an involvement in CD of the tested markers and of further undetected variation in strong linkag e disequilibrium (D' congruent to 1) with them. The power of the test, was not adequate to detect an association with an unknown polymorphism which is not in complete linkage disequilibrium with those analysed.