Behçet’s disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Sergio Burillo-Sanz, Marco-Antonio Montes-Cano, José-Raúl García-Lozano, Israel Olivas-Martínez, Norberto Ortego-Centeno, Francisco-José García-Hernández, Gerard Espinosa, Genaro Graña-Gil, Juan Sánchez-Bursón, María Rosa Juliá, Roser Solans, Ricardo Blanco, Ana-Celia Barnosi-Marín, Ricardo Gómez de la Torre, Patricia Fanlo, Mónica Rodríguez-Carballeira, Luis Rodríguez-Rodríguez, Teresa Camps, Santos Castañeda, Juan-Jose Alegre-Sancho, Javier Martín, María Francisca González-Escribano

ABSTRACT

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. More... »

PAGES

2777

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-39113-5

DOI

http://dx.doi.org/10.1038/s41598-019-39113-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112395515

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30808881


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