Abstract for presentation at 11th International Congress of Human Genetics

Candidate Gene Association Analysis of Severe Lung Injury in Pediatric Community Acquired Pneumonia

  • Julia Krushkal, University of Tennessee Health Science Center, United States
  • Kimberly Lamar, University of Tennessee Health Science Center, United States
  • Marko Puljic, University of Tennessee Health Science Center, United States
  • Peggy O'Cain, University of Tennessee Health Science Center, United States
  • Pallavi Prasad, Northwestern University, United States
  • Qing Zhang, The Children’s Foundation of Memphis Research Center, Le Bonheur Children’s Medical Center, United States
  • Melita Smith, University of Tennessee Health Science Center, United States
  • Mary Dahmer, University of Tennessee Health Science Center, United States
  • Michael Quasney, University of Tennessee Health Science Center. Children’s Foundation of Memphis Research Center, Le Bonheur Children's Medical, United States

    • Community-acquired pneumonia (CAP) – induced lung injury and subsequent acute respiratory failure significantly contribute to pediatric morbidity and mortality. Using biallelic genetic marker loci from two candidate genes, angiotensin converting enzyme (ACE) and tumor necrosis factor alpha (TNFA), we investigated the effect of genetic variation on the severity of lung injury associated with CAP. Population genetic analyses of 448 African American, Caucasian, and Hispanic children, and patients from other ethnic groups with CAP at two U.S. pediatric hospitals in Chicago, IL and Memphis, TN suggested that the ACE insertion (I)/deletion (D) polymorphism was in Hardy-Weinberg (HW) equilibrium in each ethnic sample and in the combined data set. In contrast, HW disequilibrium was suggested for the –308 A/G polymorphism near the TNFA gene. Statistical analyses showed significantly higher frequency of the ACE genotypes carrying the D allele in Caucasian children requiring mechanical ventilation (MV) than in those who did not require MV (p=0.036 for the DD genotype and 0.047 for the DI genotype). Linear modeling suggested that the presence of the DD genotype was predictive of the length of stay in pediatric intensive care units (p=0.014), along with patient ethnic background and age also being significant predictors. Borderline significance values (p=0.05), possibly due to HW disequilibrium, were obtained for the association of the TNFA –308 AG genotype with MV in Caucasians and for the effect of the AA genotype in linear modeling of acute respiratory distress syndrome stratified by ethnic background. These results suggest that the ACE D allele may directly affect or be in linkage disequilibrium with a genome site involved in CAP-induced pediatric lung injury. Possible causes of the HW disequilibrium of the TNFA –308 marker in pediatric CAP patients require further investigation.

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