Association of cystic fibrosis transmembrane conductance regulator gene variants with acute lung injury in African American children with pneumonia*.

Abstract

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.

• Authors: Julie M Baughn, Michael W Quasney, Pippa Simpson, Daniel Merchant, Shun-Hwa Li, Hara Levy, Mary K Dahmer
• Journal: Critical care medicine (Crit Care Med) Vol. 40 Issue 11 Pg. 3042-9 (Nov 2012) ISSN: 1530-0293 [Electronic] United States
• PMID: 22890249 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Cystic Fibrosis Transmembrane Conductance Regulator

Topics

• Acute Lung Injury (ethnology, genetics)
• Adolescent
• Black or African American (genetics)
• Alleles
• Base Sequence
• Child
• Child, Preschool
• Community-Acquired Infections (ethnology, genetics)
• Cystic Fibrosis Transmembrane Conductance Regulator (genetics)
• DNA Primers
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Pneumonia (ethnology, genetics)
• Polymorphism, Genetic (genetics)
• Prospective Studies