The influence of genetic variation in surfactant protein B on severe lung injury in African American children. Crit Care Med 2011 May;39(5):1138-44
Date
02/02/2011Pubmed ID
21283003DOI
10.1097/CCM.0b013e31820a9416Abstract
OBJECTIVE: To determine whether genetic variations in the gene coding for surfactant protein B are associated with lung injury in African American children with community-acquired pneumonia.
DESIGN: A prospective cohort genetic association study of lung injury in children with community-acquired pneumonia.
SETTING: Two major tertiary care children's hospitals.
SUBJECTS: African American children with community-acquired pneumonia (n = 395) either evaluated in the emergency department or admitted to the hospital.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-five African American children (14 days to 18 yrs of age) with community-acquired pneumonia were enrolled. Thirty-seven patients required mechanical ventilation and 26 of these were diagnosed with acute lung injury or acute respiratory distress syndrome. Genotyping was performed on seven linkage disequilibrium-tag single nucleotide polymorphisms in the surfactant protein B gene. Univariate analysis demonstrated two linkage disequilibrium-tag single nucleotide polymorphisms, rs1130866 (also known as SP-B + 1580 C/T) and rs3024793, were associated with the need for mechanical ventilation in African American children (p = .016 and p = .030, respectively). Multivariable analysis indicated that both of these single nucleotide polymorphisms are independently associated with need for mechanical ventilation (p = .040 and p = .012, respectively) as was rs7316 when its interaction with age was considered (p = .015). Multivariable analysis examining acute lung injury demonstrated a significant association of rs7316 with acute lung injury (p = .031). Haplotype analysis was also performed. Two haplotypes, GTGCGCG and ATATAAG, were associated with need for mechanical ventilation using either univariate (p = .041 and p = .043, respectively) or multivariable analysis (odds ratios of 2.62, p = .048, and 3.12, p = .033, respectively).
CONCLUSIONS: Genetic variations in the gene coding for surfactant protein B are associated with more severe lung injury as indicated by the association of specific single nucleotide polymorphism genotypes and haplotypes with the need for mechanical ventilation in African American children with community-acquired pneumonia.
Author List
Dahmer MK, O'cain P, Patwari PP, Simpson P, Li SH, Halligan N, Quasney MWAuthor
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
Age Distribution
Analysis of Variance
Child
Child, Preschool
Cohort Studies
Community-Acquired Infections
Emergency Service, Hospital
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Incidence
Infant
Infant, Newborn
Logistic Models
Male
Multivariate Analysis
Odds Ratio
Pneumonia
Polymorphism, Genetic
Prospective Studies
Pulmonary Surfactant-Associated Protein B
Respiration, Artificial
Severity of Illness Index
Sex Distribution
Statistics, Nonparametric
