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


METHODS
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.
El Saleeby
Chadi M
CM
Department of Pediatrics, Harvard Medical School, Massachusetts General Hospital for Children, Boston, MA 02114, USA. celsaleeby@partners.org
Li
Rongling
R
Somes
Grant W
GW
Dahmer
Mary K
MK
Quasney
Michael W
MW
DeVincenzo
John P
JP
D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D007902:Length of Stay; D008297:Male; D020641:Polymorphism, Single Nucleotide; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D012121:Respiration, Artificial; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000628:therapy; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000628:therapy; D020539:Sequence Analysis, Protein; D012720:Severity of Illness Index
D037662:Pulmonary Surfactant-Associated Protein A; C445843:SFTPA2 protein, human