Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.
Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.
Hoebee
Barbara
B
Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. b.hoebee@rivm.nl.
Bont
Louis
L
Rietveld
Edwin
E
van Oosten
Marijke
M
Hodemaekers
Hennie M
HM
Nagelkerke
Nico J D
NJ
Neijens
Herman J
HJ
Kimpen
Jan L L
JL
Kimman
Tjeerd G
TG
D000328:Adult; D001988:Bronchiolitis / Q000235:genetics*; D002648:Child; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D016906:Interleukin-9 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016906:Interleukin-9; D019948:Receptors, Interleukin-4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4