Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit

  • Neal J. Thomas
  • Mary K. Dahmer
  • Michael W. Quasney


Much progress has been made in the past decade in the understanding of the genetic contribution to the development of human disease in general, and critical care illness specifically. With the mapping of the human genome and on-going mapping of genetic polymorphisms and haplotypes in humans, the field of critical care is now in prime position to study the impact of genetics on common illnesses that affect children who require critical care, to examine how differences of the host defense response lead to variable outcomes in outwardly appearing similar disease states, and to study how genetic differences in response to therapy will help practitioners tailor therapeutic interventions to an individual child’s genetic composition. While we are still years away from true individualized medicine, we are now closer than ever to understanding why two might children respond to the same environmental insult in vastly different ways.


Septic Shock Lung Injury Angiotensin Converting Enzyme Respiratory Syncytial Virus Acute Respiratory Distress Syndrome 
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Suggested Readings

  1. Adamzik M, Frey U, Sixt S, et al. ACE I/D but not AGT (−6)A/G polymorphism is a risk factor for mortality in ARDS. Eur Respir J. 2007;29:482–8.PubMedCrossRefGoogle Scholar
  2. Binder A, Endler G, Muller M, et al. 4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia. J Thromb Haemost. 2007;5:2049–54.PubMedCrossRefGoogle Scholar
  3. Cornell TT, Wynn J, Shanley TP, et al. Mechanisms and regulation of the gene-expression response to sepsis. Pediatrics. 2010;125: 1248–58.PubMedCrossRefGoogle Scholar
  4. Fang XM, Schroder S, Hoeft A, Stuber F. Comparison of two polymorphisms of the interleukin-1 gene family: interleukin-1 receptor antagonist polymorphism contributes to susceptibility to severe sepsis. Crit Care Med. 1999;27:1330–4.PubMedCrossRefGoogle Scholar
  5. Gao L, Barnes KC. Recent advances in genetic predisposition to clinical acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2009;296:L713–25.CrossRefGoogle Scholar
  6. Gao L, Grant A, Halder I, et al. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol. 2006;34:487–95.PubMedCrossRefGoogle Scholar
  7. Gao L, Flores C, Fan-Ma S, et al. Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations. Transl Res. 2007;150:18–29.PubMedCrossRefGoogle Scholar
  8. Gong MN, Zhou W, Williams PL, et al. Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome. Crit Care Med. 2007;35:48–56.PubMedCrossRefGoogle Scholar
  9. Harding D, Baines PB, Brull D, et al. Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism. Am J Respir Crit Care Med. 2002;165: 1103–6.PubMedGoogle Scholar
  10. Lin Z, Pearson C, Chinchilli V, et al. Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clin Genet. 2000;58:181–91.PubMedCrossRefGoogle Scholar
  11. Lin Z, Thomas NJ, Wang Y, et al. Deletions within a CA-repeat-rich region of intron 4 of the human SP-B gene affect mRNA splicing. Biochem J. 2005;389:403–12.PubMedCrossRefGoogle Scholar
  12. Mandelberg A, Tal G, Naugolny L, et al. Lipopolysaccharide hyporesponsiveness as a risk factor for intensive care unit hospitalization in infants with respiratory syncitial virus bronchiolitis. Clin Exp Immunol. 2006;144:48–52.PubMedCrossRefGoogle Scholar
  13. Manocha S, Russell JA, Sutherland AM, et al. Fibrinogen-beta gene haplotype is associated with mortality in sepsis. J Infect. 2007;54:572–7.PubMedCrossRefGoogle Scholar
  14. Menges T, Konig IR, Hossain H, et al. Sepsis syndrome and death in trauma patients are associated with variation in the gene encoding for tumor necrosis factor. Crit Care Med. 2008;36:1456–62.PubMedCrossRefGoogle Scholar
  15. Mira JP, Cariou A, Grall F, et al. Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA. 1999;282:561–8.PubMedCrossRefGoogle Scholar
  16. Nadel S, Newport MJ, Booy R, Levin M. Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from meningococcal disease. J Infect Dis. 1996;174: 878–80.PubMedCrossRefGoogle Scholar
  17. Quasney MW, Waterer GW, Dahmer MK, et al. Association between surfactant protein B  +  1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia. Crit Care Med. 2004;32:1115–9.PubMedCrossRefGoogle Scholar
  18. Shanley TP, Cvijanovich N, Lin R, et al. Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock. Mol Med. 2007;13(9-10):495–508.PubMedCrossRefGoogle Scholar
  19. Simon BA, Easley RB, Grigoryev DN, et al. Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2006;291:L851–61.PubMedCrossRefGoogle Scholar
  20. Sorensen TI, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med. 1988;318:727–32.PubMedCrossRefGoogle Scholar
  21. The National Human Genome Research Institute’s Talking Glossary of Genetic Terms.
  22. Toubiana J, Courtine E, Pene F, et al. IRAK1 functional genetic variant affects severity of septic shock. Crit Care Med. 2010;38: 2287–94.PubMedCrossRefGoogle Scholar
  23. Wong HR, Shanley TP, Sakthivel B, et al. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007;30: 146–55.PubMedCrossRefGoogle Scholar
  24. Ye SQ, Simon BA, Maloney JP, et al. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. Am J Respir Crit Care Med. 2005;171:361–70.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2012

Authors and Affiliations

  • Neal J. Thomas
    • 1
  • Mary K. Dahmer
    • 2
  • Michael W. Quasney
    • 2
  1. 1.Pediatric Critical Care Medicine, Department of PediatricsPenn State College of Medicine, Penn State Hershey Children’s HospitalHersheyUSA
  2. 2.Pediatric Critical Care Medicine, Department of PediatricsMedical College of Wisconsin, Children’s Hospital of WisconsinMilwaukeeUSA

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