Genetic Susceptibility to Life-threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants
Autor: | Laura Beatriz Talarico, Patricio Leandro Acosta, Barbara Carrizo, Ana Clara Giordano, Eduardo Walter Yfran, Florencia Feldman, Analia Toledano, E.L. Lopez, Fausto M Ferolla, Ana Caratozzolo, María M. Contrini |
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Rok vydání: | 2020 |
Předmět: |
Male
Myxovirus Resistance Proteins Microbiology (medical) Single-nucleotide polymorphism Respiratory Syncytial Virus Infections Polymorphism Single Nucleotide Virus 03 medical and health sciences 0302 clinical medicine 030225 pediatrics Genetic predisposition Humans Medicine Genetic Predisposition to Disease Prospective Studies 030212 general & internal medicine Receptors Immunologic Prospective cohort study Genotyping business.industry Infant Odds ratio Viral Load Immunity Innate Toll-Like Receptor 4 Macrophage receptor with collagenous structure Infectious Diseases Toll-Like Receptor 8 Pediatrics Perinatology and Child Health Immunology Female business Child Hospitalized Viral load |
Zdroj: | Pediatric Infectious Disease Journal. 39:1057-1061 |
ISSN: | 0891-3668 |
Popis: | Background Genetic background may be an important host determinant of respiratory syncytial virus (RSV) disease severity, but full characterization of susceptibility genes remains unclear. This study aimed to assess the presence of specific single-nucleotide polymorphisms (SNPs) in selected genes codifying for different components of the antiviral innate immune response, to determine their role for developing RSV life-threatening disease (LTD). Methods Prospective cohort study including previously healthy full-term infants hospitalized with a first RSV infection during 2017-2018. RSV detection, quantification and subgroup determination, and genotyping for SNPs in Toll-like receptor 4 (TLR4 rs4986790, rs4986791), Toll-like receptor 8 (TLR8 rs3761624), macrophage receptor with collagenous structure(MARCO rs1318645) and myxovirus resistance 1(MX1 rs469390) were performed by real-time polymerase chain reaction in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit requiring ventilatory support. Results Seventy-five patients were studied, 15 (20%) developed LTD. Infants with concurrent SNPs in MX1 and TLR8, MARCO and TLR8 or MARCO, MX1 and TLR8 had an increased risk of developing LTD. Multivariable logistic regression analysis confirmed this significant association (odds ratio [OR] = 3.75, P = 0.046; OR = 3.92, P = 0.040; OR = 5.56, P = 0.010, respectively). No differences were seen in viral load of patients with LTD compared with those with better outcome (P = 0.737). In addition, no differences in viral load were seen in patients with the described high-risk SNPs compared with those without these polymorphisms. Conclusions Life-threatening RSV infection in previously healthy infants was significantly associated with the presence of combined SNPs in MARCO, MX1 and TLR8. |
Databáze: | OpenAIRE |
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