Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population

J Pediatr. 2010 Mar;156(3):409-14. doi: 10.1016/j.jpeds.2009.09.043. Epub 2009 Nov 14.

Abstract

Objective: To examine whether genetic variations within the surfactant protein A2 (SP-A2) gene are associated with respiratory syncytial virus (RSV) disease severity in infected children.

Study design: Naturally infected children aged < or =24 months were prospectively enrolled in 3 RSV seasons. SP-A2 genotyping was performed. Independent clinical predictors of disease severity were analyzed. The association of SP-A2 genetic diversity and disease severity was tested by using multivariate logistic regression models and 4 levels of disease gradation as outcome measures.

Results: Homozygosity of the 1A(0) allele was protective against hospitalization (odds ratio [OR] = 0.15, P = .0010). This remained significant in African American patients (OR = 0.24, P = .042) and Caucasian patients (OR = 0.05, P = .021) after adjustment for other co-variates. Hospitalized children with the 1A(2) allele demonstrated significant protection from severe disease with univariate analyses, but only a trend for protection with multivariate analyses. Patients homozygous or heterozygous for an asparagine at amino acid position 9 were twice or more likely to need intensive care unit admission (OR = 2.15, P = .022), require intubation (OR = 3.04, P = .005), and have a hospitalization lasting > or =4 days (OR = 1.89, P = .02) compared with children homozygous for a threonine at this position.

Conclusions: SP-A2 polymorphisms are associated with the severity of RSV infection in infants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Female
  • Gene Frequency
  • Genotype
  • Hospitalization*
  • Humans
  • Infant
  • Intensive Care Units, Pediatric
  • Length of Stay
  • Male
  • Polymorphism, Single Nucleotide*
  • Pulmonary Surfactant-Associated Protein A / genetics*
  • Respiration, Artificial
  • Respiratory Syncytial Virus Infections / genetics*
  • Respiratory Syncytial Virus Infections / therapy
  • Respiratory Tract Infections / genetics*
  • Respiratory Tract Infections / therapy
  • Sequence Analysis, Protein
  • Severity of Illness Index

Substances

  • Pulmonary Surfactant-Associated Protein A
  • SFTPA2 protein, human