Association of cystic fibrosis transmembrane conductance regulator gene variants with acute lung injury in African American children with pneumonia*.
OBJECTIVE
The cystic fibrosis transmembrane conductance regulator regulates fluid balance in alveolar epithelial cells and appears to modulate the inflammatory response. To determine whether more severe lung injury in children who develop community-acquired pneumonia is associated with variations known to affect function in the gene coding for cystic fibrosis transmembrane conductance regulator.


METHODS
A prospective cohort genetic association study of lung injury in children with community-acquired pneumonia.


METHODS
Three major tertiary care children's hospitals.


METHODS
Caucasian and African American children with community-acquired pneumonia either evaluated in the emergency department or admitted to the hospital.


METHODS
None.


RESULTS
Caucasian and African American children with pneumonia were genotyped for the most common variants reported to affect cystic fibrosis transmembrane conductance regulator function, the p.508del mutation, the (TG)mTn variable repeat region, and the M470V polymorphism in the cystic fibrosis transmembrane conductance regulator gene. Genotypes and haplotypes were determined, and the association of high-risk alleles or high-risk haplotypes (defined as the presence of at least one variant known to decrease the level of functional cystic fibrosis transmembrane conductance regulator) with the need for mechanical ventilation or the development of acute lung injury was evaluated. Forty-two children in the Caucasian cohort (n = 304) required mechanical ventilation; 32 developed acute lung injury. Forty-three children in the African American cohort (n = 474) required mechanical ventilation; 29 developed acute lung injury. In African American children, high-risk (TG)mTn alleles known to result in decreased levels of functional cystic fibrosis transmembrane conductance regulator were associated with the need for mechanical ventilation (p = .0013) and the development of acute lung injury (p = .0061). Multivariable analysis demonstrated that high-risk (TG)mTn alleles were independently associated with mechanical ventilation (odds ratios = 3.19; 95% confidence interval, 1.63-6.26) and acute lung injury (odds ratios = 3.36; 95% confidence interval, 1.50-7.53) in African American children.


CONCLUSIONS
Genetic variation in cystic fibrosis transmembrane conductance regulator is associated with acute lung injury in African American children with community-acquired pneumonia.
Section of Pulmonary and Sleep Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Julie M
JM
Baughn
Michael W
MW
Quasney
Pippa
P
Simpson
Daniel
D
Merchant
Shun-Hwa
SH
Li
Hara
H
Levy
Mary K
MK
Dahmer
D055371:Acute Lung Injury / Q000208:ethnology / Q000235:genetics*; D000293:Adolescent; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000208:ethnology / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011014:Pneumonia / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies
D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator