J Pediatr Intensive Care 2020; 09(04): 241-247
DOI: 10.1055/s-0040-1709658
Original Article

Glucocorticoid Receptor Polymorphisms in Children Undergoing Congenital Heart Surgery with Cardiopulmonary Bypass

1  Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, United States
2  Division of Critical Care, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
,
Ilias Iliopoulos
3  Department of Pediatrics, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
,
4  Division of Cardiology, Department of Pediatrics, Advocate Children's Hospital, Chicago, Illinois, United States
,
2  Division of Critical Care, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
,
Rashmi D. Sahay
5  Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
,
Lin Fei
5  Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
,
David S. Cooper
3  Department of Pediatrics, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
› Author Affiliations

Abstract

We conducted a candidate gene association study to test the hypothesis that different gene polymorphisms will be associated with corticosteroid responsiveness and study outcomes among children undergoing congenital heart surgery. This is a prospective observational cohort study at a large, tertiary pediatric cardiac center on children undergoing corrective or palliative congenital heart surgery. A total of 83 children were enrolled. DNA was isolated for three polymorphisms of interest namely N363 (rs56149945) and 9β (rs6198) associated with increased sensitivity to corticosteroids and BclI (rs41423247) associated with decreased sensitivity to corticosteroids. Duration of inotropic use, low cardiac output scores (LCOS), and vasoactive inotrope scores were examined in relation to these three polymorphisms. Using Kaplan–Meier analysis, heterozygous individuals showed longer transcriptional intermediary factor (TIF) compared with wild type for N363 polymorphism (p = 0.05). In multivariable Cox regression, heterozygous alleles for 9β polymorphism showed significantly shorter TIF compared with wild type (hazard ratio = 2.04 [1.08–3.87], p = 0.03). The relationship between lower LCOS scores and alleles groups was significant for 9β heterozygous polymorphism only (1.5 [1–2.2], p = 0.01) in comparison to wild type and homozygous. The presence of heterozygote alleles for the increased corticosteroid sensitivity is associated with longer TIF compared with wild type. Conversely, the presence of heterozygous alleles for the decreased sensitivity to corticosteroids is associated with shorter TIF compared with wild type.



Publication History

Received: 06 January 2020

Accepted: 10 March 2020

Publication Date:
29 April 2020 (online)

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