Analysis of β-defensin and Toll-like receptor gene copy number variation in celiac disease

• Published in: Human immunology 2010-08, Vol.71 (8), p.833-836
• Main Authors: Fernandez-Jimenez, Nora, Castellanos-Rubio, Ainara, Plaza-Izurieta, Leticia, Gutierrez, Galder, Castaño, Luis, Vitoria, Juan Carlos, Bilbao, Jose Ramon
• Format: Article
• Language: English
• Subjects: Adult; Allergy and Immunology; beta-Defensins - genetics; Celiac disease; Celiac Disease - genetics; Child, Preschool; Copy number variation; Female; Gene Dosage; Gene Frequency; Genetic predisposition; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Male; Toll-like receptor; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 4 - genetics; Toll-Like Receptors - genetics; β-defensin
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2010.05.012

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. β-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 β-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. β-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.