title: Analysis of beta-defensin and Toll-like receptor gene copy number variation in celiac disease.
abstract: Celiac disease (CD) is an immune-mediated disorder of the gut in which innate and adaptive responses are involved. Toll-like receptor (TLR) 2 and TLR4 participate in host defense through antigen recognition, and show altered expression in CD gut mucosa. beta-defensins are inducible antimicrobial peptides, and DEFB gene copy number polymorphisms have been associated with autoimmune and inflammatory disorders. We performed copy number analysis of TLR2, TLR4, and the beta-defensin cluster (DEFB4, DEFB103 and DEFB104) by gene-specific, real-time polymerase chain reaction (PCR) in 376 CD patients and 376 controls. TLR genes did not show copy number variation, and all samples presented with two copies. beta-defensin clusters varied between 2 and 9 copies per genome, and when grouped into bins, high copy numbers (>4) were underrepresented among patients (p = 0.023; odds ratio = 0.69, 95% CI = 0.50-0.96), suggesting that increased copy numbers could protect from CD, possibly by impeding bacterial infiltration more efficiently and preserving gut epithelial integrity.
authors.affiliation: Endocrinology, Diabetes and Nutrition Research Group, Hospital de Cruces, Barakaldo-Bizkaia, Basque Country, Spain.
authors.forename: Nora
authors.initials: N
authors.lastname: Fernandez-Jimenez
authors.forename: Ainara
authors.initials: A
authors.lastname: Castellanos-Rubio
authors.forename: Leticia
authors.initials: L
authors.lastname: Plaza-Izurieta
authors.forename: Galder
authors.initials: G
authors.lastname: Gutierrez
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: D000328:Adult; D002446:Celiac Disease / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D023083:beta-Defensins / Q000235:genetics*
chemical_list: C106641:DEFB4A protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D023083:beta-Defensins