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.
They 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.
Dysfunctional melatonin receptors result in altered melatonin signaling. Two membrane melatonin receptors, MT1 and MT2, and nuclear receptors have been identified and found to be active in humans.
Multiple studies have investigated the melatonin receptor 1B gene, MTNR1B, polymorphisms. The minor allele, G, of the single nucleotide polymorphism (SNP) rs10830963, occurs in 30% of people of European descent and has been associated with altered melatonin signaling leading to multiple pathologies.
One prior perspective, a cohort study has investigated the relationship between the risk genotype and delirium. However, the analysis yielded 93% of subjects having the minor allele calling into question the methods or generalizability of that sample population.
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.
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.
This observation suggests a role of the 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.