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Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4

Genes & Immunity volume 8, pages 171–176 (2007)Cite this article

Abstract

Genome-wide scans have detected linkage to celiac disease (CD) in several genomic locations, including 19q13.4. Killer immunoglobulin-like receptor (KIR) genes map to the region and encode receptors of natural killer (NK) cells and certain T cells that modulate cytolitic activity through interactions with HLA class I ligands, participating in the innate immune response. We performed KIR genotyping in a group of 70 CD patients of Basque origin and compared gene content, genotype and haplotype frequencies to ethnically matched blood-donors. The frequency of gene combination KIR2DL5B+/KIR2DL5A− was significantly higher in the disease group, and this result was confirmed in a second group of 343 CD patients and 160 controls of Spanish origin, suggesting an implication of this ‘unexpressed’ gene with increased susceptibility to CD (combined OR of 3.63 (95% CI: 1.76–7.51; P=0.0004)), possibly due to the lack of an efficient inhibitory signal. Our results support the role of the KIR gene cluster in celiac disease and replicate the CD-susceptibility locus at 19q13.4.

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Acknowledgements

This work was partially funded by Grants 03/11032 from the Basque Department of Health and PI04/1170 from the Instituto de Salud Carlos III of the Spanish Ministry of Health. IS is a predoctoral fellow supported by a grant from the University of the Basque Country. GPN is a FIS researcher supported by the Spanish Ministry of Health grant 03/0064. JRB is a co-funded by the Spanish Ministry of Health-Human Resources Stabilization Program.

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Authors and Affiliations

  1. Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Bizkaia, Spain

    I Santin, A Castellanos-Rubio, G Perez de Nanclares, L Castaño & J R Bilbao

  2. Pediatric Gastroenterology Unit, Hospital de Cruces, Barakaldo, Bizkaia, Spain

    J C Vitoria

  3. Department of Pediatrics, University of the Basque Country, Bilbao, Spain

    J C Vitoria & L Castaño

  4. Department of Nursing, University of the Basque Country, Bilbao, Spain

    J R Bilbao

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  1. I Santin
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Correspondence to J R Bilbao.

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Santin, I., Castellanos-Rubio, A., Perez de Nanclares, G. et al. Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4. Genes Immun 8, 171–176 (2007). https://doi.org/10.1038/sj.gene.6364367

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