Validation of association of the apolipoprotein e ε2 allele with neurodevelopmental dysfunction after cardiac surgery in neonates and infants

J. William Gaynor*, Daniel Seung Kim, Cammon B. Arrington, Andrew M. Atz, David C. Bellinger, Amber A. Burt, Nancy S. Ghanayem, Jeffery P. Jacobs, Teresa M. Lee, Alan B. Lewis, William T. Mahle, Bradley S. Marino, Stephen G. Miller, Jane W. Newburger, Christian Pizarro, Chitra Ravishankar, Avni B. Santani, Nicole S. Wilder, Gail P. Jarvik, Seema MitalMark W. Russell

*Corresponding author for this work

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Objective Apolipoprotein E (APOE) genotype is a determinant of neurologic recovery after brain ischemia and traumatic brain injury. The APOE ε2 allele has been associated with worse neurodevelopmental (ND) outcome after repair of congenital heart defects (CHD) in infancy. Replication of this finding in an independent cohort is essential to validate the observed genotype-phenotype association.

Results Complete data were available for 298 of 435 patients. After adjustment for preoperative and postoperative covariates, the APOE ε2 allele was associated with a lower PDI score (P =.038). Patients with the ε2 allele had a PDI score approximately 6 points lower than those without the risk allele, explaining 1.04% of overall PDI variance, because the ε2 allele was present in only 11% of the patients. There was a marginal effect of the ε2 allele on MDI scores (P =.058).

Conclusions These data validate the association of the APOE ε2 allele with adverse early ND outcomes after cardiac surgery in infants, independent of patient and operative factors. Genetic variants that decrease neuroresilience and impair neuronal repair after brain injury are important risk factors for ND dysfunction after surgery for CHD.

Original languageEnglish (US)
Pages (from-to)2560-2568
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume148
Issue number6
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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    Gaynor, J. W., Kim, D. S., Arrington, C. B., Atz, A. M., Bellinger, D. C., Burt, A. A., Ghanayem, N. S., Jacobs, J. P., Lee, T. M., Lewis, A. B., Mahle, W. T., Marino, B. S., Miller, S. G., Newburger, J. W., Pizarro, C., Ravishankar, C., Santani, A. B., Wilder, N. S., Jarvik, G. P., ... Russell, M. W. (2014). Validation of association of the apolipoprotein e ε2 allele with neurodevelopmental dysfunction after cardiac surgery in neonates and infants. Journal of Thoracic and Cardiovascular Surgery, 148(6), 2560-2568. https://doi.org/10.1016/j.jtcvs.2014.07.052