Behçet's disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes
Burillo-Sanz, Sergio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Montes-Cano, Marco-Antonio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
García-Lozano, J. R. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Olivas-Martínez, I. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Ortego-Centeno, Norberto (Hospital Universitario San Cecilio (Granada))
García-Hernández, Francisco-José (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Espinosa, G. (Hospital Clínic i Provincial de Barcelona)
Graña-Gil, G. (Department of Rheumatology. Complejo Hospitalario Universitario)
Sánchez-Bursón, J. (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Juliá, María Rosa (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Solans, Roser (Hospital Universitari Vall d'Hebron)
Blanco, Ricardo (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Barnosi-Marín, Ana-Celia (Complejo Hospitalario Torrecárdenas (Almeria))
Gómez de la Torre, Ricardo (Hospital Universitario Central de Asturias)
Fanlo, Patricia (Hospital Virgen del Camino (Pamplona))
Rodríguez-Carballeira, M. (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Rodriguez-Rodriguez, Luis (Hospital Clínico San Carlos (Madrid))
Camps i Miró, Teresa (Department of Internal Medicine. Hospital Regional Universitario)
Castañeda, Santos (Instituto de Investigación Hospital Universitario de la Princesa)
Alegre-Sancho, Juan José (Hospital Universitari Doctor Peset (València))
Martín, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
González-Escribano, M. F. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p. Gln703Lys, NOD2 p. Arg702Trp and p. Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27. 6%) carried at least one rare variant and 13 of them (3. 7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0. 003). A suggestive protective association of the minor allele of NOD2 p. Arg702Trp (P = 0. 01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p. Arg702Trp would be independent of HLA.
Ayudas:	Instituto de Salud Carlos III PI16/01373
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Scientific reports, Vol. 9 Núm. 1 (january 2019) , p. 2777, ISSN 2045-2322

DOI: 10.1038/s41598-019-39113-5
PMID: 30808881

8 p, 1.1 MB

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