David, SusanaCastro, LilianaDuarte, ElsaGaspar, UlissesRodrigues, Maria Rosário da CostaCueto-Rojo, Maria VanessaMendonça, JoanaFerrão, JoséMachado, MiguelPoças, JoséLavinha, JoãoVieira, LuísSantos, Ana SofiaElsevier2025-11-122025-11-122025-03-08Hum Immunol. 2025 May;86(3):111271. doi: 10.1016/j.humimm.2025.111271. Epub 2025 Mar 80198-8859http://hdl.handle.net/10400.18/10592Q fever is a highly contagious zoonosis capable of causing large outbreaks of important health and economic consequences. Host genetic factors are believed to influence the development of severe chronic Q fever following the infection by the etiological agent, Coxiella burnetii. Targetted next generation sequencing (NGS) was performed in a case-control genetic association study on 53 confirmed Q fever cases, including 38 compatible with acute and 15 with chronic disease, and 29 samples from the general Portuguese population. Four SNPs in the IFNGR2 locus, rs78407108 G > A, rs17879956 C > T, rs7277167 C > T, and rs9974603 C > A, showed a statistically significant association to chronic Q fever, resisting the Bonferroni correction. These belonged to haplotypes significantly associated with chronic Q fever. The individual SNPs are referenced in the GTEx database as possible eQTLs. Given the direct bearing of IFNGR2 on IFN-γ signaling, the possible involvement of the associated variants with higher IFNGR2 expression could be in line with observations suggesting that IFN-γ production in chronic Q fever patients is significantly higher than in healthy controls. Further investigations are required to clarify the role of IFNGR2 signaling in association with chronic Q fever.engChronic Q feverIFNGR2IFN-γ signalingCandidate Gene Association StudyHaplotypeNext Generation SequencingChronic DiseaseInfecções Sistémicas e Zoonosesjournal article10.1016/j.humimm.2025.1112711879-116640056764