John Smythe

Publications (2)7.17 Total impact

• Article: Factors Influencing Participation in a Population-based Biorepository for Childhood Heart Disease.

  Tanya Papaz, Mina Safi, Ashok-Kumar Manickaraj, Carly Ogaki, Jennifer Breaton Kyryliuk, Liz Burrill, Christine Dodge, Catherine Chant-Gambacort, Laura-Lee Walter, Herschel Rosenberg, Tapas Mondal, John Smythe, Jane Lougheed, Lynn Bergin, Elaine Gordon, David Chitayat, Erwin Oechslin, Seema Mital
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  ABSTRACT: BACKGROUND:Consenting minors for genetics research and biobanking involves ethical and social challenges. We examined factors influencing participation rates in a population-based biorepository for childhood heart disease.METHODS:Individuals were prospectively enrolled across 7 centers in Ontario by using a standardized consent form. Individuals were approached for consent for the donation of blood/saliva (DNA), tissue, and skin from the affected individual for future genomics and stem cell research. Consent rates were compared between pediatric and adult patients and factors affecting consent were analyzed by using multiple logistic regression analysis.RESULTS:From 2008 to 2011, 3637 patients were approached. A total of 2717 pediatric patients consented (90% consent rate); mean age was 8.5 ± 5.8 years (57% male; 76% white). A total of 561 adult patients consented (92% consent rate, P = .071 versus pediatric). Factors associated with lower pediatric consent rates included younger age, race, absence of complex defects, and location of consent; these were not associated with adult consent rates. Leading causes for refusal of consent were lack of interest in research (43%), overwhelmed clinically (14%), and discomfort with genetics (11%). Concerns related to privacy, insurability, indefinite storage, and ongoing access to medical records were not the leading causes for refusal.CONCLUSIONS:The high pediatric consent rate (90%) was comparable with that of adults. Ethical, social, or legal issues were not the leading reasons for refusal of consent.
  PEDIATRICS 10/2012; · 4.47 Impact Factor
• Article: Genetic determinants of right-ventricular remodeling after tetralogy of Fallot repair.

  Aamir Jeewa, Ashok Kumar Manickaraj, Luc Mertens, Cedric Manlhiot, Caroline Kinnear, Tapas Mondal, John Smythe, Herschel Rosenberg, Jane Lougheed, Brian W McCrindle, Glen van Arsdell, Andrew N Redington, Seema Mital
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  ABSTRACT: Background:Hypoxia-inducible factor (HIF1A) regulates the myocardial response to hypoxia and hemodynamic load. We investigated the association of HIF1A variants with right-ventricular (RV) remodeling after tetralogy of Fallot (TOF) repair.Methods:Children with TOF were genotyped for three single-nucleotide polymorphisms in HIF1A. Genotypes were analyzed for association with RV myocardial protein expression and fibrosis at complete repair (n = 42) and RV dilation, fractional area change, and freedom from pulmonary valve/conduit replacement on follow-up.Results:In 180 TOF patients, mean age at repair was 1.0 ± 0.8 y with follow-up at 9.0 ± 3.5 y; 82% had moderate to severe pulmonary insufficiency. Freedom from RV reinterventions at 5, 10, and 15 y was 92, 84, and 67%, respectively. Patients with more functioning HIF1A alleles had higher transforming growth factor β1 expression and more fibrosis at initial repair as compared with controls (P < 0.05). During follow-up, patients with more functioning HIF1A alleles showed less RV dilation, better preservation of RV function, and greater freedom from RV reinterventions (P < 0.05). This was confirmed in a replication cohort of 69 patients.Conclusion:In children who have had TOF repair, a lower number of functioning HIF1A alleles was associated with RV dilation and dysfunction, suggesting that hypoxia adaptation in unrepaired TOF may influence RV phenotype after repair.
  Pediatric Research 07/2012; 72(4):407-13. · 2.70 Impact Factor