title: Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children.
abstract: Prostaglandin I(2) (PGI(2)) protects against RSV-induced illness in mice. A variable-number tandem repeat (VNTR) polymorphism has been detected in the promoter region of the PGI(2) synthase (PGIS) gene. We sought to determine if PGI(2) 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 PGI(2). 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 PGI(2) metabolite concentrations. The urinary PGI(2) 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 PGI(2) concentrations during RSV LRTI, and severity of RSV infection in previously healthy infants.
authors.affiliation: School of Medicine, Fukushima Medical University, Fukushima, Japan. don@fmu.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Tebeb
authors.initials: T
authors.lastname: Gebretsadik
authors.forename: Tina V
authors.initials: TV
authors.lastname: Hartert
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakata
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Katayose
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sakuma
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Hosoya
authors.forename: Ray Stokes
authors.initials: RS
authors.lastname: Peebles
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suzutani
mesh_terms: D000328:Adult; D002673:Child, Hospitalized; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D011464:Epoprostenol / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats; D011401:Promoter Regions, Genetic; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology* / Q000821:virology*; D012141:Respiratory Tract Infections / Q000473:pathology* / Q000821:virology*; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase