title: Linkage disequilibrium between intra-locus variants in the aminopeptidase n gene and test of their association with coeliac disease.
abstract: Coeliac disease (CD) is a multigenic and multifactorial enteropathy triggered by gluten-composing proteins. A possible involvement of the intestinal Aminopeptidase N (APN) was investigated by an association analysis. SSCP analysis detected four variants at position 281, 378, 956 and 2957 (referred to no. g178535, GenBank) that were studied in 193 Italian CD families. The haplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D' = D/Dmax) between the polymorphic sites were calculated. Significant D' values ranged between 0.78 and 0.31. Association with CD was tested by TDT (Transmission Disequilibrium Test) utilizing as markers the nucleotide substitutions and their haplotypic combinations. No statistically 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 linkage disequilibrium (D' approximately equal 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.
authors.affiliation: Dipartimento di Scienze Mediche, Università del Piemonte Orientale Amedeo Avogadro, Novara, Italy. giordano@med.no.unipmn.it
authors.forename: M
authors.initials: M
authors.lastname: Giordano
authors.forename: E
authors.initials: E
authors.lastname: Bolognesi
authors.forename: S
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: M
authors.initials: M
authors.lastname: Lessi
authors.forename: P
authors.initials: P
authors.lastname: Zavattari
authors.forename: G
authors.initials: G
authors.lastname: Oderda
authors.forename: F
authors.initials: F
authors.lastname: Clot
authors.forename: S
authors.initials: S
authors.lastname: Percopo
authors.forename: G
authors.initials: G
authors.lastname: Casari
authors.forename: L
authors.initials: L
authors.lastname: Greco
authors.forename: R
authors.initials: R
authors.lastname: Tosi
authors.forename: P
authors.initials: P
authors.lastname: Momigliano-Richiardi
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D018826:CD13 Antigens / Q000235:genetics*; D002446:Celiac Disease / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D018076:DNA, Complementary; D018826:CD13 Antigens