Reframing the Biological Basis of Neuroprotection Using Functional Genomics: Differentially Weighted, Time-Dependent Multifactor Pathogenesis of Human Ischemic Brain Damage
Kofke, William A; Ren, Yue; Augoustides, John G; Li, Hongzhe; Nathanson, Katherine; Siman, Robert; Meng, Qing Cheng; Bu, Weiming; Yandrawatthana, Sukanya; Kositratna, Guy; Kim, Cecilia; Bavaria, Joseph E
PMCID:6028620
PMID: 29997569
ISSN: 1664-2295
CID: 5994082
Does the melatonin receptor 1B gene polymorphism have a role in postoperative delirium?
Mahanna-Gabrielli, Elizabeth; Miano, Todd A; Augoustides, John G; Kim, Cecilia; Bavaria, Joseph E; Kofke, W Andrew
INTRODUCTION:Patients undergoing cardiac surgery are at high risk for postoperative delirium, which is associated with longer hospital and intensive care lengths of stays, increased morbidity and mortality. Because sleep disturbances are common in delirium, melatonin has been an area of interest in the treatment of delirium. The rs10830963 single nucleotide polymorphism of the melatonin receptor 1B gene can cause pathological dysfunction of this receptor and is associated with delayed morning offset of melatonin. We hypothesized patients undergoing aortic cardiac surgery who have the risk genotype of a melatonin receptor 1B polymorphism would have a higher incidence of postoperative delirium. METHODS:Ninety-eight patients undergoing aortic root or valve surgery underwent analysis for melatonin receptor 1B single nucleotide polymorphism, rs10830963. Using a validated method, CHART-DEL, all charts were retrospectively reviewed and scored for the presence of delirium while blinded to the results of the melatonin receptor 1B gene polymorphism. RESULTS:Genotyping for melatonin receptor 1B polymorphism was acceptable in 76 subjects of European descent of which 18 (23.7%) had delirium. Four of seven subjects with the risk genotype had delirium versus only 20.3% of subjects without the risk genotype. This carried an odds ratio of 5.2 (1.0, 26.1), p = 0.050. CONCLUSION:This observation suggests a role of the risk genotype of a melatonin receptor 1B polymorphism in the development of postoperative delirium. These hypotheses generating results warrant further prospective studies in a larger cohort group with delirium, circadian rhythm and melatonin assessments.
PMCID:6258533
PMID: 30481216
ISSN: 1932-6203
CID: 5994092