Filemón Bucardo1, Yaoska Reyes1, Marlen Morales1, Rafaela Briceño2, Fredman González1, Åke Lundkvist3, Lennart Svensson4,5, Johan Nordgren4. 1. Department of Microbiology, Faculty of Medical Science, National Autonomous University of Nicaragua, León, Nicaragua (UNAN-León). 2. Sistema Local de Atención Integral en Salud, Ministry of Health León, León, Nicaragua. 3. Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 4. Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 5. Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Abstract
BACKGROUND: Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya. METHODS: To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays. RESULTS: After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively). CONCLUSION: This study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.
BACKGROUND: Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya. METHODS: To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays. RESULTS: After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively). CONCLUSION: This study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.
Authors: Thaise Yasmine Vasconcelos de Lima Cavalcanti; Mylena Ribeiro Pereira; Sergio Oliveira de Paula; Rafael Freitas de Oliveira Franca Journal: Viruses Date: 2022-05-05 Impact factor: 5.818
Authors: Natalia Redondo; Isabel Rodríguez-Goncer; Patricia Parra; Francisco López-Medrano; Esther González; Ana Hernández; Hernando Trujillo; Tamara Ruiz-Merlo; Rafael San Juan; María Dolores Folgueira; Amado Andrés; José María Aguado; Mario Fernández-Ruiz Journal: Sci Rep Date: 2022-07-05 Impact factor: 4.996