Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children

Prostaglandin I2 (PGI2) protects against RSV-induced illness in mice. A variable-number tandem repeat (VNTR) polymorphism has been detected in the promoter region of the PGI2 synthase (PGIS) gene. We sought to determine if PGI2 concentrations or polymorphisms of the PGIS gene correlate with severity of RSV lower respiratory tract infections (LRTI) in human infants. VNTR polymorphisms were studied in 81 previously healthy children between birth and 12 months of age who were hospitalized for LRTI due to RSV and 98 healthy adult control subjects. The severity of RSV infection was quantified using a clinical scoring system, and infant urine samples were collected during the acute illness for measurement of the urinary metabolite of PGI2. There were no significant differences in the overall distribution of alleles and genotypes between infants with RSV LRTI and the control subjects. The severity of RSV infection significantly inversely correlated with urinary PGI2 metabolite concentrations. The urinary PGI2 metabolite concentration correlated with the number of VNTR. The presence of a genotype with a low number VNTR repeats significantly correlated with the most severe RSV LRTI, and genotypes with the highest number of VNTR correlated with the least severe RSV LRTI. A functional polymorphism in the promoter region of the PGIS gene is associated with both significant differences in urinary PGI2 concentrations during RSV LRTI, and severity of RSV infection in previously healthy infants. J. Med. Virol. 80:2015–2022, 2008. © 2008 Wiley-Liss, Inc.