RT Journal Article SR Electronic T1 Variants of the IFI16 Gene Affecting the Levels of Expression of mRNA Are Associated with Susceptibility to Behçet Disease JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 695 OP 701 DO 10.3899/jrheum.140949 VO 42 IS 4 A1 Lourdes Ortiz-Fernández A1 José-Raúl García-Lozano A1 Marco-Antonio Montes-Cano A1 Marta Conde-Jaldón A1 Norberto Ortego-Centeno A1 Francisco-José García-Hernández A1 Gerard Espinosa A1 Genaro Graña-Gil A1 Juan Sánchez-Bursón A1 Ricardo Blanco A1 Ana-Celia Barnosi-Marín A1 Roser Solans A1 Patricia Fanlo A1 Mónica Rodríguez-Carballeira A1 Teresa Camps A1 Santos Castañeda A1 Antonio Núñez-Roldán A1 Javier Martín A1 María-Francisca González-Escribano YR 2015 UL http://www.jrheum.org/content/42/4/695.abstract AB 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.