title: A regulatory single nucleotide polymorphism in the ubiquitin D gene associated with celiac disease.
abstract: An aberrant immune response triggered by dietary gluten is the main driving force underlying celiac disease (CD), but other biologic pathways that are dysregulated also participate in disease development. Genetic variation within these pathways might influence expression, contributing to susceptibility to CD. We have investigated the implication of ubiquitin D (UBD), a member of the ubiquitin-proteasome system that is strongly upregulated in the intestinal mucosa of active CD. Reverse transcriptase-polymerase chain reaction analysis of intestinal biopsy sample pairs (at diagnosis vs treated) from 30 CD patients confirmed overexpression of UBD in active disease tissue (fold change = 8.3; p = 0.0022). In silico prediction tools identified rs11724 as a putative regulatory single nucleotide polymorphism and association analysis of 468 CD patients and 459 controls revealed that the minor rs11724*C allele was more frequent among patients (minor allele frequency = 0.44 vs 0.39; odds ratio [OR] = 1.23; p = 0.028) and suggested a dominant allele effect (OR = 1.49; p = 0.0045). Correlation of the rs11724 genotype and UBD mRNA levels (OR = 0.76; p = 0.0021) further supports its implication in disease development.
authors.affiliation: Immunogenetics Research Laboratory, Hospital de Cruces, Barakaldo-Bizkaia, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Castellanos-Rubio
authors.forename: Izortze
authors.initials: I
authors.lastname: Santin
authors.forename: Iñaki
authors.initials: I
authors.lastname: Irastorza
authors.forename: Felix
authors.initials: F
authors.lastname: Sanchez-Valverde
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Vitoria
authors.forename: Jose Ramon
authors.initials: JR
authors.lastname: Bilbao
mesh_terms: D001706:Biopsy; D002446:Celiac Disease / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014452:Ubiquitins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C109184:UBD protein, human; D014452:Ubiquitins