Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications.
Mol Med Rep
; 25(6)2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35445734
ABSTRACT
Patients undergoing major surgery experience postoperative inflammation, which may contribute to postoperative morbidity. Endogenous glucocorticoids (GCs) are an essential part of the stress response, but this response varies between individuals, which may in turn affect clinical outcome and specifically postoperative inflammation. Exon 1 of the NR3C1 gene, encoding the GC receptor (GR), contains an established region of differential regulation. DNA methylation patterns in this region have been found to differ between individuals. The present study investigated the methylation status and genotype in the cytosinephosphateguanine (CpG) island in exon 1 of NR3C1 in 24 patients [Median age 65.5 (range 4281) years, 11 male, 13 female] who underwent major abdominal (12 pancreatic, 12 hepatic) surgery and explored its association with postoperative complications. DNA was extracted from peripheral blood leukocytes and underwent targeted bisulfite sequencing of the CpG island. Complications were graded according to the ClavienDindo classification and 14 out of 24 patients had postoperative complications. Multifactorial and partial least square analyses were used to analyse the data. A homogenous demethylated pattern was observed in all patients and no single CpG methylation was associated with postoperative complications. Four SNPs were significantly associated with higher ClavienDindo scores. Genetic variability in the chromosome 5143,402,505143,405,805 region of exon 1 of the GR gene NR3C1, but not DNA methylation, was associated with more severe postoperative complications in patients having major abdominal surgery. These results indicated that the patients' response to GCs may be of clinical importance for inflammatory conditions.
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MEDLINE
Assunto principal:
Receptores de Glucocorticoides
/
Glucocorticoides
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article