Increased RNA editing in children with cyanotic congenital heart disease

Abstract

Purpose: To test the hypothesis that RNA editing is altered in pediatric patients with cyanotic congenital heart disease (CHD) and to determine whether A-to-I RNA editing is associated with the postoperative course following cardiac surgery. Cyanotic CHD is associated with a unique pathophysiology caused by chronic hypoxia. The perioperative course of cyanotic infants is partly dictated by the degree of expression of inflammatory and cardiac genes, some of which undergo A-to-I RNA editing.

Methods: RNA was extracted pre- and postoperatively from blood samples of cyanotic and acyanotic patients. Each sample was analyzed for A-to-I RNA editing using automatic DNA sequencing of an intronic segment of the MED13 gene. RNA expression levels of adenosine deaminase acting on RNA (ADAR) enzymes responsible for RNA editing were examined by quantitative reverse-transcriptase polymerase chain reaction.

Results: A-to-I RNA editing in MED13 was significantly higher among cyanotic patients (n = 19) than acyanotic ones (n = 18) both pre- and postoperatively, as manifested by average editing at seven highly edited sites (27.4 ± 8.5% versus 20.8 ± 10.2%; P = 0.038) and editing at specific sites, e.g., position 14 (20.2 ± 5.1% versus 14.5 ± 5.2%; P = 0.002). Cyanotic patients exhibited a more complicated postoperative course than acyanotic patients. ADAR2 RNA levels were significantly lower among cyanotic patients.

Conclusions: Cyanotic children manifest significantly higher rates of A-to-I RNA editing than acyanotic children as well as a more complicated surgical course. Posttranscriptional RNA changes may affect cellular and metabolic pathways and influence the perioperative course following hypoxia.