TY - JOUR
T1 - Behçet’s disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes
AU - Burillo-Sanz, Sergio
AU - Montes-Cano, Marco Antonio
AU - García-Lozano, José Raúl
AU - Olivas-Martínez, Israel
AU - Ortego-Centeno, Norberto
AU - García-Hernández, Francisco José
AU - Espinosa, Gerard
AU - Graña-Gil, Genaro
AU - Sánchez-Bursón, Juan
AU - Juliá, María Rosa
AU - Solans, Roser
AU - Blanco, Ricardo
AU - Barnosi-Marín, Ana Celia
AU - Gómez de la Torre, Ricardo
AU - Fanlo, Patricia
AU - Rodríguez-Carballeira, Mónica
AU - Rodríguez-Rodríguez, Luis
AU - Camps, Teresa
AU - Castañeda, Santos
AU - Alegre-Sancho, Juan Jose
AU - Martín, Javier
AU - González-Escribano, María Francisca
PY - 2019/2/26
Y1 - 2019/2/26
N2 - © 2019, The Author(s). 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.
AB - © 2019, The Author(s). 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.
UR - http://www.mendeley.com/research/beh%C3%A7ets-disease-genetic-interactions-between-hlab51-variants-genes-autoinflammatory-syndromes
U2 - 10.1038/s41598-019-39113-5
DO - 10.1038/s41598-019-39113-5
M3 - Article
C2 - 30808881
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
M1 - 2777
ER -