Interleukin-1 receptor antagonist intron 2 variable number of tandem repeats polymorphism and respiratory failure in children with community-acquired pneumonia.
OBJECTIVE
To determine whether the variable nucleotide tandem repeat polymorphism in intron 2 of the interleukin-1 receptor antagonist gene is associated with lung injury in children with community-acquired pneumonia.


METHODS
A prospective cohort of children diagnosed with community-acquired pneumonia.


METHODS
Two pediatric hospitals.


METHODS
Eight hundred fifty pediatric patients with community-acquired pneumonia were enrolled.


METHODS
Genotyping of the variable nucleotide tandem repeat polymorphism in intron 2 of the interleukin-1 receptor antagonist gene was performed on DNA isolated from whole blood.


RESULTS
The requirement for positive pressure ventilation or the diagnosis of acute lung injury or acute respiratory distress syndrome were the main outcomes of the study. Children (14 days-19 yrs) with community-acquired pneumonia (850) were enrolled; analysis was limited to African American (515) and Caucasian (232) patients. Of the 82 patients requiring positive pressure ventilation, 44 were diagnosed with acute lung injury or acute respiratory distress syndrome. Multivariate logistic regression analyses indicated that children without a copy of the A1 allele of the variable nucleotide tandem repeat polymorphism in intron 2 of the interleukin-1 receptor antagonist gene were more likely to need positive pressure ventilation compared to those with one or two copies of this allele (odds ratio = 2.65, confidence interval, 1.02-6.90). In addition, the absence of the A1 allele also appeared to be associated with the development of community-acquired pneumonia-induced acute lung injury/acute respiratory distress syndrome (odds ratio = 3.1, confidence interval, 0.99-9.67).


CONCLUSIONS
In children with community-acquired pneumonia, absence of the A1 allele at the interleukin-1 receptor antagonist intron 2 polymorphic site is associated with increased risk for more severe lung injury, as measured by the need for positive pressure ventilation or the development of acute lung injury or acute respiratory distress syndrome. Conversely, presence of the A1 allele is associated with decreased risk for more severe lung injury in this patient population.
Department of Pediatrics, Division of Critical Care, Children's Memorial Hospital, Northwestern University, Evanston, IL, USA.
Pallavi P
PP
Patwari
Peggy
P
O'Cain
Denise M
DM
Goodman
Melita
M
Smith
Julia
J
Krushkal
Caiquin
C
Liu
Grant
G
Somes
Michael W
MW
Quasney
Mary K
MK
Dahmer
D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D007438:Introns; D008297:Male; D018598:Minisatellite Repeats; D011014:Pneumonia / Q000235:genetics*; D011175:Positive-Pressure Respiration; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000628:therapy; D055815:Young Adult
D053590:Interleukin 1 Receptor Antagonist Protein