The Journal of Pediatrics
Volume 156, Issue 3 , Pages 409-414.e4, March 2010

Surfactant Protein A2 Polymorphisms and Disease Severity in a Respiratory Syncytial Virus-Infected Population

  • Chadi M. El Saleeby, MD

      Affiliations

    • Departments of Pediatrics and Pediatric Infectious Diseases, Harvard Medical School, Massachusetts General Hospital for Children, Boston, MA
    • University of Tennessee School of Medicine, Department of Pediatrics, Memphis, TN
    • Department of Preventive Medicine, University of Tennessee School of Medicine, Memphis, TN
    • LeBonheur Children's Medical Center, Memphis, TN
    • The Children's Foundation Research Center, Memphis, TN
    • St. Jude Children's Research Hospital, Department of Infectious Diseases, Memphis, TN
    • Corresponding Author InformationReprint requests: Chadi El Saleeby, MD, Division of Pediatric Infectious Diseases, Department of Pediatrics, Massachusetts General Hospital for Children, 175 Cambridge St, CPZS 548, Boston, MA 02114.
    • ,
  • Rongling Li, PhD

      Affiliations

    • Department of Preventive Medicine, University of Tennessee School of Medicine, Memphis, TN
    • ,
  • Grant W. Somes, PhD

      Affiliations

    • Department of Preventive Medicine, University of Tennessee School of Medicine, Memphis, TN
    • ,
  • Mary K. Dahmer, PhD

      Affiliations

    • Division of Pediatric Critical Care, Department of Pediatrics, Medical College of Wisconsin, and the Children's Research Institute, Milwaukee, WI
    • ,
  • Michael W. Quasney, MD, PhD

      Affiliations

    • Division of Pediatric Critical Care, Department of Pediatrics, Medical College of Wisconsin, and the Children's Research Institute, Milwaukee, WI
    • ,
  • John P. DeVincenzo, MD

      Affiliations

    • University of Tennessee School of Medicine, Department of Pediatrics, Memphis, TN
    • LeBonheur Children's Medical Center, Memphis, TN
    • The Children's Foundation Research Center, Memphis, TN
    • University of Tennessee Graduate School of Health Sciences, Department of Molecular Sciences, Memphis, TN

Received 17 December 2008; received in revised form 10 August 2009; accepted 15 September 2009. published online 16 November 2009.

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 ≤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 1A0 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 1A2 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 ≥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.

OR, Odds ratio, RSV, Respiratory syncytial virus, SNP, Single-nucleotide polymorphism, SP-A2, Surfactant protein A2

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 Supported by the following grants to J.D.: National Institutes of Health (RR 16187) from the National Center for Research Resources, the Children's Foundation Research Center of Memphis, The University of Tennessee General Clinical Research Center (UHPHS RR00211), and the LeBonheur Foundation. C.E.S. supported by a fellowship grant from The American Lebanese Syrian Associated Charities and St Jude Children's Research Hospital. None of the study sponsors had any role in the study design, the collection, analysis, and interpretation of data, the writing of the report and the decision to submit the manuscript for publication. The authors declare no conflicts of interest.

PII: S0022-3476(09)00923-8

doi:10.1016/j.jpeds.2009.09.043

Refers to article:

  • The Pulmonary Collectins and Respiratory Syncytial Virus: Is There a Clinical Link?

    Paul S. Kingma, Jeffrey A. Whitsett
    The Journal of Pediatrics March 2010 (Vol. 156, Issue 3, Pages 349-350)

The Journal of Pediatrics
Volume 156, Issue 3 , Pages 409-414.e4, March 2010

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