Lourdes Ortiz-Fernández1, José-Raúl García-Lozano1, Marco-Antonio Montes-Cano1, Marta Conde-Jaldón1, Norberto Ortego-Centeno1, Francisco-José García-Hernández1, Gerard Espinosa1, Genaro Graña-Gil1, Juan Sánchez-Bursón1, Ricardo Blanco1, Ana-Celia Barnosi-Marín1, Roser Solans1, Patricia Fanlo1, Mónica Rodríguez-Carballeira1, Teresa Camps1, Santos Castañeda1, Antonio Núñez-Roldán1, Javier Martín1, María-Francisca González-Escribano1. 1. From the Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Sevilla, Sevilla; Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada; Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla; Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona; Servicio de Reumatología, Complejo Hospitalario Universitario, La Coruña; Servicio de Reumatología, Hospital Universitario de Valme, Sevilla; Servicio de Reumatología, Hospital Marqués de Valdecilla, Santander; Servicio de Medicina Interna, Hospital de Torrecárdenas, Almería; Servicio de Medicina Interna, Hospital Vall d'Hebron, Barcelona; Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona; Servicio de Medicina Interna, Hospital Universitari Mútua, Terrassa; Servicio de Medicina Interna, Hospital Universitario Carlos Haya, Málaga; Servicio de Reumatología, Hospital de la Princesa, Madrid; Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, Spain.L. Ortíz-Fernández, BSc; J.R. García-Lozano, MD, PhD; M.A. Montes-Cano, PhD; M. Conde-Jaldón, BSc; A. Núñez-Roldán, MD, PhD; M.F. González-Escribano, PhD; Servicio de Inmunología, Hospital Universitario Virgen del Rocío; N. Ortego-Centeno, MD, Servicio de Medicina Interna, Hospital Clínico San Cecilio; F.J. García-Hernández, MD, Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío; G. Espinosa, MD, Servicio de Enfermedades Autoinmunes, Hospital Clinic; G. Graña-Gil, MD, Servicio de Reumatología, Complejo Hospitalario Universitario; J. Sánchez-Bursón, MD, Servicio de Reumatología, Hospital Universitario de Valme; R. Blanco, MD, Servicio de Reumatología, Hospital Marqués de Valdecilla; A-C. Barnosi-Marín, MD, Servicio de Medicina Interna, Hospital de Torrecárdenas; R. Solans, MD, Servicio de Medicina Interna, Hospital Vall d'Hebron; P. Fanlo, MD, Servicio de Medi
Abstract
OBJECTIVE: Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD. METHODS: Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively. RESULTS: Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06-1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47-0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027). CONCLUSION: Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.
OBJECTIVE: Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD. METHODS: Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively. RESULTS:Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06-1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47-0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027). CONCLUSION: Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.
Authors: Karen V Swanson; Mustafa Girnary; Tomaz Alves; Jenny Py Ting; Kimon Divaris; Jim Beck; Carolina Maschietto Pucinelli; Raquel Assed Bezerra da Silva; Dilek Uyan; Justin E Wilson; William T Seaman; Jennifer Webster-Cyriaque; Nishma Vias; Yizu Jiao; Lloyd Cantley; Arnaud Marlier; Roland R Arnold; Julie T Marchesan Journal: J Periodontol Date: 2022-06-10 Impact factor: 4.494
Authors: Julie T Marchesan; Mustafa Saadat Girnary; Kevin Moss; Eugenia Timofeev Monaghan; Grant Joseph Egnatz; Yizu Jiao; Shaoping Zhang; Jim Beck; Karen V Swanson Journal: Periodontol 2000 Date: 2020-02 Impact factor: 7.589