title: Transmission of surfactant protein variants and haplotypes in children hospitalized with respiratory syncytial virus.
abstract: Severity of lung injury with respiratory syncytial virus (RSV) infection is variable and may be related to genetic variations. This preliminary report describes a prospective, family-based association study of children hospitalized secondary to RSV, aimed to determine whether intragenic and other haplotypes of surfactant proteins (SP)-A and SP-D are transmitted disproportionately from parents to offspring with RSV disease. Genomic DNA was genotyped for several SP-A and SP-D single nucleotide polymorphisms (SNPs). Transmission disequilibrium test analysis was used to determine transmission of variants and haplotypes from parents to affected offspring. Three hundred seventy-five individuals were studied, including 148 children with active RSV disease and one or both parents. The SP-A2 intragenic haplotype 1A was found to be protective (p = 0.013). The SP-D SNP DA160_A may possibly be an "at-risk" marker (p = 0.0058). Additional two- and three-marker haplotypes were associated with severe RSV disease, with two being protective (DA11_T/DA160_G and DA160_G/SP-A2 1A/SP-A1 6A). We conclude that there may be associations between SP-A and SP-D and RSV disease. Further study is required to determine whether these variants can be used to target a high-risk patient population in clinical trials aimed at reducing either the symptoms of acute infection or long-term pulmonary sequelae.
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Susan
authors.initials: S
authors.lastname: DiAngelo
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Hess
authors.forename: Ruzong
authors.initials: R
authors.lastname: Fan
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Ball
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Geskey
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Willson
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics*
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D