Polymorphisms in the Catechol-O-Methyltransferase Gene and Delirium in the Elderly

Munster, Barbara C. Van; Baas, Frank; Tanck, Michael W.T.; Rooij, Sophia E. J. A. de

doi:10.1159/000327353

Cited by 8 publications

(7 citation statements)

References 41 publications

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“…The absence of an association between COMT and postoperative delirium is consistent with one other study that examined this relationship. 19 In the latter work, polymorphisms in three single nucleotide polymorphisms (SNPs) on the COMT gene (rs4680 [examined in the current study], rs4818, and rs6269) were not associated with the development of delirium in older adults admitted to a medical department or to a surgical department post hip fracture. 19 We focused on only one SNP given its primary association with cognitive and neuropsychological vulnerability, and did find a modestly lower risk of delirium among COMT warriors, but this did not achieve statistical significance.…”

Section: Discussionmentioning

confidence: 78%

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The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype

Vasunilashorn

Ngo

Jones

et al. 2019

The American Journal of Geriatric Psychiatry

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Objectives: Catechol-O-methyltransferase (COMT), a key enzyme in degrading stress hormones, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated “warriors”) withstand the onset of neuropsychiatric disorders and cognitive decline, while individuals with Met/Met and Val/Met genotypes (“non-warriors”) are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium. Design: Prospective cohort. Setting: Two academic medical centers. Participants: 547 patients age ≥70 undergoing major non-cardiac surgery. Measurements: We collected blood, extracted DNA, and performed COMT genotyping using allele specific PCR assays, considering warriors vs. non-warriors. High plasma CRP, measured on postoperative day 2 (POD2) using ELISA, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, and surgery type, stratified by COMT genotype, to determine whether the association between CRP and delirium differs by COMT. Results: Prevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk[RR] 1.0, 95% confidence interval[CI] 0.4–2.6). In contrast, among non-warriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1–2.2). Conclusions: COMT warriors may be protected against the increased risk of delirium associated with high POD2 CRP. With further confirmation, COMT genotype may help to target interventions for delirium prevention to the vulnerable non-warrior group.

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Section: Discussionmentioning

confidence: 78%

“…These strengths distinguish our study from previous work on COMT and delirium. 19 Additional study strengths include our state-of-the-art measures of delirium and nearly complete capture of data on COMT genotype and CRP across the population (98%).…”

Section: Discussionmentioning

confidence: 99%

The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype

Vasunilashorn

Ngo

Jones

et al. 2019

The American Journal of Geriatric Psychiatry

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“…Perturbations in executive function can result in delirium, which affects mainly attention, and dementia, which affects mainly memory. Although COMT does not appear to influence delirium directly [34], it modified the known association between C-reactive protein (CRP), an acute phase reactant, and postoperative delirium [35]. Aging also influences cognition and among a biracial cohort of elders, COMT was associated with rate of cognitive decline with the val-allele having a protective effect [24].…”

Section: Neurological Conditions Deliriummentioning

confidence: 96%

“…Perturbations in executive function can result in delirium which affects mainly attention, and dementia which affects mainly memory. Although COMT does not appear to directly influence delirium, it modified the known association between C-reactive protein (CRP), an acute phase reactant, and postoperative delirium [34,35] Functional pain disorders A recent meta-analyses of COMT and functional pain disorders found that the low-activity met-allele was associated with fibromyalgia. An earlier meta-analysis also found that the met-allele was associated with fibromyalgia and widespread chronic pain, but not migraine headache or chronic musculoskeletal pain conditions [36,37] Chronic fatigue syndrome Chronic fatigue syndrome patients were more likely to be homozygous for the met-allele compared with val-allele carriers [38,39] Pain COMT low-activity haplotypes were associated with greater sensitivity to nociceptive, but lower sensitivity to neuropathic pain.…”

Section: Deliriummentioning

confidence: 99%

Systems Pharmacogenomics – Gene, Disease, Drug and Placebo Interactions: A Case Study in COMT

2019

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Disease, drugs and the placebos used as comparators are inextricably linked in the methodology of the double-blind, randomized controlled trial. Nonetheless, pharmacogenomics, the study of how individuals respond to drugs based on genetic substrate, focuses primarily on the link between genes and drugs, while the link between genes and disease is often overlooked and the link between genes and placebos is largely ignored. Herein, we use the example of the enzyme catechol-O-methyltransferase to examine the hypothesis that genes can function as pharmacogenomic hubs across system-wide regulatory processes that, if perturbed in randomized controlled trials, can have primary and combinatorial effects on drug and placebo responses.

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“…Patients were excluded if they were unable to speak or understand Dutch or English. The institutional medical ethics committee approved the study [22].…”

Section: Patients and Proceduresmentioning

confidence: 99%

Polymorphisms in the Melatonin Receptor 1B Gene and the Risk of Delirium

Jonghe¹,

Rooij²,

Tanck

et al. 2012

Dement Geriatr Cogn Disord

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Background/Aims: A disturbed sleep-wake rhythm cycle can be seen in delirium and as melatonin regulates this cycle via melatonin receptors, genetic variations in these receptors may contribute to susceptibility to delirium. The purpose of this study was to investigate whether genetic variants in the melatonin receptor 1B (MTNR1B) gene are associated with delirium. Methods: Elderly medical and hip surgery patients were included in the study. Five single-nucleotide polymorphisms (SNPs) were determined in the MTNR1B gene, i.e. rs18030962, rs3781638, rs10830963, rs156244 and rs4753426. Results: In total, 53% of 171 hip fracture patients and 33% of 699 medical patients were diagnosed with delirium. None of the polymorphisms were found to be associated with the occurrence of delirium. Conclusion: Future research could focus on sequencing this gene to look for other functional SNPs in relation to delirium.

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Polymorphisms in the Catechol-O-Methyltransferase Gene and Delirium in the Elderly

Cited by 8 publications

References 41 publications

The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype

The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype

Systems Pharmacogenomics – Gene, Disease, Drug and Placebo Interactions: A Case Study in COMT

Polymorphisms in the Melatonin Receptor 1B Gene and the Risk of Delirium

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