title: Haplotypes of surfactant protein C are associated with common paediatric lung diseases.
abstract: Surfactant protein C is part of the surfactant complex lining up the alveoles and thereby inhibiting collapse of the airways. In addition it is involved in innate immune responses. Rare polymorphisms within surfactant protein C have been linked to sporadic paediatric lung diseases, like proteinosis or interstitial lung diseases. One study in the Finnish population described association of common polymorphisms with neonatal respiratory syndrome. Other common lung diseases have not yet been investigated for association with this gene. The aim of this study was to test surfactant protein C for association with bronchial asthma and with severe respiratory syncytial virus associated diseases in infancy. The two common amino acid variants Asn138Thr and Asn186Ser were genotyped on 322 children with asthma, 131 children with severe respiratory syncytial virus associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage's trend test; haplotypes were calculated with FAMHAP and FASTEHPLUS. Polymorphisms were in Hardy-Weinberg equilibrium and in tight linkage equilibrium in all populations. Single polymorphisms showed no association with the diseases, however, surfactant protein C haplotypes were associated with severe respiratory syncytial virus associated diseases (p = 0.013). Furthermore, an inverse haplotype distribution was found between children with asthma and respiratory syncytial virus infection (p = 0.00025). The results of our study might suggest opposing roles of surfactant Protein C in the genetic predisposition for respiratory syncytial virus associated diseases vs. asthma. The causal mechanism for this observation has still to be shown.
authors.affiliation: University Children's Hospital, University of Freiburg, Freiburg, Germany.
authors.forename: Beena
authors.initials: B
authors.lastname: Puthothu
authors.forename: Marcus
authors.initials: M
authors.lastname: Krueger
authors.forename: Jessica
authors.initials: J
authors.lastname: Heinze
authors.forename: Johannes
authors.initials: J
authors.lastname: Forster
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinzmann
mesh_terms: D000328:Adult; D000367:Age Factors; D001249:Asthma / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008171:Lung Diseases / Q000209:etiology* / Q000235:genetics; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000209:etiology / Q000235:genetics
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human