The enzymatic activities of brain catechol‐<scp>O</scp>‐methyltransferase (<scp>COMT</scp>) and methionine sulphoxide reductase are correlated in a <scp>COMT V</scp>al/<scp>M</scp>et allele‐dependent fashion

Moskovitz, Jackob; Walss‐Bass, Consuelo; Cruz, Dianne A.; Thompson, Peter M.; Hairston, Jenaqua; Bortolato, Marco

doi:10.1111/nan.12219

Cited by 10 publications

(12 citation statements)

References 72 publications

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“…Qualitative synthesis showed that findings were inconsistent, were not replicated, or lacked statistical evidence to substantiate reported genotype differences (Table S11 in Supplement 2). (20)(21)(22)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)…”

Section: No Consistent Evidence For Functional Polymorphisms In Dopammentioning

confidence: 99%

Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1–5, MAOA, MAOB, TH, VMAT1, and VMAT2

Tunbridge

Narajos

Harrison

et al. 2019

Biological Psychiatry

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BACKGROUND: Many polymorphisms in dopamine genes are reported to affect cognitive, imaging, or clinical phenotypes. It is often inferred or assumed that such associations are causal, mediated by a direct effect of the polymorphism on the gene product itself. However, the supporting evidence is not always clear. METHODS: We conducted systematic reviews and meta-analyses to assess the empirical evidence for functional polymorphisms in genes encoding dopaminergic enzymes (COMT, DBH, DDC, MAOA, MAOB, and TH), dopamine receptors (DRD1, DRD2, DRD3, DRD4, and DRD5), the dopamine transporter (DAT), and vesicular transporters (VMAT1 and VMAT2). We defined functionality as an effect of the polymorphism on the expression, abundance, activity, or affinity of the gene product. RESULTS: We screened 22,728 articles and identified 255 eligible studies. We found robust and medium to large effects for polymorphisms in 4 genes. For catechol-O-methyltransferase (COMT), the Val 158 Met polymorphism (rs4680) markedly affected enzyme activity, protein abundance, and protein stability. Dopamine b-hydroxylase (DBH) activity was associated with rs1611115, rs2519152, and the DBH-STR polymorphism. Monoamine oxidase A (MAOA) activity was associated with a 5 0 VNTR polymorphism. Dopamine D 2 receptor (DRD2) binding was influenced by the Taq1A (rs1800497) polymorphism, and rs1076560 affected DRD2 splicing. CONCLUSIONS: Some widely studied dopaminergic polymorphisms clearly and substantially affect the abundance or activity of the encoded gene product. However, for other polymorphisms, evidence of such an association is negative, inconclusive, or lacking. These findings are relevant when selecting polymorphisms as "markers" of dopamine function, and for interpreting the biological plausibility of associations between these polymorphisms and aspects of brain function or dysfunction.

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Section: No Consistent Evidence For Functional Polymorphisms In Dopammentioning

confidence: 99%

Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1–5, MAOA, MAOB, TH, VMAT1, and VMAT2

Tunbridge

Narajos

Harrison

et al. 2019

Biological Psychiatry

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“…The present study was conducted on the same postmortem brain tissues used in a previous study (Moskovitz et al, 2015). All demographic and clinical characteristics of the individuals are described in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Genomic DNA was extracted from brain tissue and COMT rs4680 genotyping was performed as previously indicated (Moskovitz et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

“…Postmortem human brain sections were homogenized as described above and their COMT activity was monitored as previously indicated in Moskovitz et al (2015).…”

Section: Methodsmentioning

confidence: 99%

“…The resulting mutation is a valine ( Val )-to-methionine ( Met ) transition, which leads to a significant reduction of catalytic activity in vitro (Moskovitz et al, 2015). We recently showed that the functional deficits in Met variants may be partially contributed by the sulfoxidation of this amino acid mediated by oxidative stress (Egan et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Manic symptom severity correlates with COMT activity in the striatum: A post-mortem study

Bortolato

Walss‐Bass

Thompson³

et al. 2016

The World Journal of Biological Psychiatry

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Objectives The enzyme catechol-O-methyl transferase (COMT), which catalyzes the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity. Nevertheless, the specific relevance of COMT enzymatic activity in the pathophysiology of BD and schizophrenia dimensions remains elusive. Methods We measured COMT catalytic activity in post-mortem prefrontal cortices, striata and cerebella of schizophrenia and BD patients, as well as non-affected controls. These values were then correlated with rs4680 genotypes and psychopathology scores in the last week of life. Results No direct correlation between COMT activity and rs4680 genotypes was found; however, the severity of manic symptoms was highly correlated with COMT activity in the striatum, irrespective of the diagnostic group. Conclusions These results suggest that COMT striatal activity, but not rs4680 genotype, may serve as a biomarker for manic symptoms. Future studies are warranted to confirm these findings and assess the neurobiological links between COMT striatal activity and manic symptoms.

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Transdermal Nanomedicines for Reduction of Dose and Site-Specific Drug Delivery

Mukherjee

Sengupta

Banerjee

et al. 2020

Nano Medicine and Nano Safety

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The enzymatic activities of brain catechol‐O‐methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele‐dependent fashion

Cited by 10 publications

References 72 publications

Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1–5, MAOA, MAOB, TH, VMAT1, and VMAT2

Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1–5, MAOA, MAOB, TH, VMAT1, and VMAT2

Manic symptom severity correlates with COMT activity in the striatum: A post-mortem study

Transdermal Nanomedicines for Reduction of Dose and Site-Specific Drug Delivery

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