UNLABELLED: Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathogenic mechanisms are unclear. Interleukin-4/Interleukin-13 (IL-4/IL-13) pathway is involved in both conditions. A common host genetic susceptibility may exist in patients whom RSV will trigger severe illness and those who develop recurrent wheezing. OBJECTIVE: To assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children. A cohort of 118 RSV-infected infants was analyzed and followed for one year. Severity of acute infection and later recurrent wheezing were characterized. Alleles and genotypes frequencies were determined for two SNP in each of the genes IL-4, IL-13 and IL-4Rα. Association tests and interaction analyses were performed. Enrollment included 60 moderate and 58 severe cases. Two SNP were found associated to severity during acute infection in IL-4Rα gene (Gln551Arg, Ile50Val). The follow up was completed in 71% of patients (84/118). Later recurrent wheezing was 54% in severe group, versus 31% in moderate cases (p=0.035). In relation to outcome, allele Ile50 in IL-4Rα was more frequent in patients with moderate disease and no wheezing outcome. A common protector genotype is proposed for Chilean children: IL-4Rα Ile/Ile. CONCLUSION: Genetic variations in the host are associated to infection severity and outcome. A common genetic background might be influencing both pathologies.
UNLABELLED: Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathogenic mechanisms are unclear. Interleukin-4/Interleukin-13 (IL-4/IL-13) pathway is involved in both conditions. A common host genetic susceptibility may exist in patients whom RSV will trigger severe illness and those who develop recurrent wheezing. OBJECTIVE: To assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children. A cohort of 118 RSV-infectedinfants was analyzed and followed for one year. Severity of acute infection and later recurrent wheezing were characterized. Alleles and genotypes frequencies were determined for two SNP in each of the genes IL-4, IL-13 and IL-4Rα. Association tests and interaction analyses were performed. Enrollment included 60 moderate and 58 severe cases. Two SNP were found associated to severity during acute infection in IL-4Rα gene (Gln551Arg, Ile50Val). The follow up was completed in 71% of patients (84/118). Later recurrent wheezing was 54% in severe group, versus 31% in moderate cases (p=0.035). In relation to outcome, allele Ile50 in IL-4Rα was more frequent in patients with moderate disease and no wheezing outcome. A common protector genotype is proposed for Chilean children: IL-4Rα Ile/Ile. CONCLUSION: Genetic variations in the host are associated to infection severity and outcome. A common genetic background might be influencing both pathologies.
Authors: Adam D Kenney; James A Dowdle; Leonia Bozzacco; Temet M McMichael; Corine St Gelais; Amanda R Panfil; Yan Sun; Larry S Schlesinger; Matthew Z Anderson; Patrick L Green; Carolina B López; Brad R Rosenberg; Li Wu; Jacob S Yount Journal: Annu Rev Genet Date: 2017-08-30 Impact factor: 16.830
Authors: Jonatan J Carvajal; Andrea M Avellaneda; Camila Salazar-Ardiles; Jorge E Maya; Alexis M Kalergis; Margarita K Lay Journal: Front Immunol Date: 2019-09-12 Impact factor: 7.561
Authors: Amanda J Driscoll; S Hasan Arshad; Louis Bont; Steven M Brunwasser; Thomas Cherian; Janet A Englund; Deshayne B Fell; Laura L Hammitt; Tina V Hartert; Bruce L Innis; Ruth A Karron; Gayle E Langley; E Kim Mulholland; Patrick K Munywoki; Harish Nair; Justin R Ortiz; David A Savitz; Nienke M Scheltema; Eric A F Simões; Peter G Smith; Fred Were; Heather J Zar; Daniel R Feikin Journal: Vaccine Date: 2020-01-20 Impact factor: 3.641