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A2868 - Genetic Variants in Human Respiratory Virus Receptors Were Associated with Infection, Recovery and Recurrence of Wheezing Exacerbations in Children
Author Block: L. Harris1, R. Allcock2, N. Kresoje3, P. N. Le Souef3, I. A. Laing1; 1University of Western Australia/Telethon Kids Institute, Perth, Australia, 2University of Western Australia/QEII Medical Centre, Perth, Australia, 3University of Western Australia, Perth, Australia.
Introduction/Aim: Human rhinoviruses (RV) and respiratory syncytial virus (RSV) are common respiratory viruses in children with acute wheezing illnesses. Viruses use human receptors to enter host cells. RSV uses nucleolin (NCL), and RV uses intercellular adhesion molecule 1 (ICAM1), low density lipoprotein receptor (LDLR) or cadherin related family member 3 (CDHR3). We aimed to assess whether variants in viral receptor genes were associated with asthma severity.
Methods: Cohort: Children who presented to a tertiary children’s hospital emergency department with acute asthma (n=50). Samples: Nasal samples for RV detection. DNA was extracted from peripheral blood. Analysis: Viral receptor genes were sequenced using Ion AmpliSeq primers (Thermo Fisher Scientific). Data collected included: (1) number of hours from presentation to discharge, (2) number of respiratory hospital presentations and admissions from birth and (3) number of salbutamol doses administered in the first 6 hours. Statistical analysis was completed using SPSS version 22. All analyses were adjusted for age and gender.
Results: The mean age of children was 8.44yrs, 60% male, 56% with detectable RV. Children with genotypes CDHR3 rs34426483 GC or CC and NCL rs7598759 CC were 0.161-0.105 fold less likely to have rhinovirus detected at recruitment than children with the other genotypes (95% confidence interval (CI): 0.023-1.11; p-value: 0.064 and 95% CI: 0.009-1.24; p-value: 0.073, respectively). Children with ICAM1 rs281437 TT genotypes had 17.0 fold more hospital visits before recruitment (95% CI: -0.062-23.5; p-value: 0.002) and took 2.52 fold longer to be discharged from hospital (95% CI: 7.81-129; p-value: 0.019) compared to children with CC genotypes. Children with ICAM1 rs5498 GG genotypes had 0.593 fold fewer treatment doses in 6 hours (95% CI: -0.852-12.1; p-value: 0.013) than children with AA genotypes.
Conclusion: Gene variants in viral receptor genes may play a role in viral infection and treatment response, and thus recurrent respiratory illnesses requiring presentation to hospital.