Association of cystic fibrosis transmembrane conductance regulator gene variants with acute lung injury in African American children with pneumonia*. Crit Care Med 2012 Nov;40(11):3042-9
Date
08/15/2012Pubmed ID
22890249Pubmed Central ID
PMC4273667DOI
10.1097/CCM.0b013e31825d8f73Scopus ID
2-s2.0-84868209535 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
OBJECTIVES: 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.
DESIGN: A prospective cohort genetic association study of lung injury in children with community-acquired pneumonia.
SETTING: Three major tertiary care children's hospitals.
SUBJECTS: Caucasian and African American children with community-acquired pneumonia either evaluated in the emergency department or admitted to the hospital.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN 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.
CONCLUSION: Genetic variation in cystic fibrosis transmembrane conductance regulator is associated with acute lung injury in African American children with community-acquired pneumonia.
Author List
Baughn JM, Quasney MW, Simpson P, Merchant D, Li SH, Levy H, Dahmer MKAuthor
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acute Lung InjuryAdolescent
Alleles
Base Sequence
Child
Child, Preschool
Community-Acquired Infections
Cystic Fibrosis Transmembrane Conductance Regulator
DNA Primers
Female
Humans
Infant
Infant, Newborn
Male
Pneumonia
Polymorphism, Genetic
Prospective Studies
