Association between the catechol‐O‐methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population

Shibata, Nobuto; Nagata, Tomoyuki; Tagai, Kenji; Shinagawa, Shunichiro; Ohnuma, Tohru; Kawai, Eri; Kasanuki, Koji; Shimazaki, Hiromi; Toda, Aiko; Tagata, Yuko; Nakada, Tomoko; Nakayama, Keiichi I.; Arai, Heii

doi:10.1002/gps.4237

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Val allele (G allele) in COMT gene that results in lower dopamine levels in synaptic cleft was associated with increased risk for AD [47]. COMT Val158Met polymorphism was compared with genetic biomarkers of AD, such as apolipoprotein E (APOE) [48][49][50][51], and with neuroimaging biomarkers of AD [52][53][54]. However, the association of COMT Val158Met polymorphism with CSF AD biomarkers was not previously tested, and case-control studies on association of COMT Val158Met polymorphism and AD yielded incon-sistent results.…”

Section: Discussionmentioning

confidence: 99%

“…However, the association of COMT Val158Met polymorphism with CSF AD biomarkers was not previously tested, and case-control studies on association of COMT Val158Met polymorphism and AD yielded incon-sistent results. The G allele in COMT Val158Met polymorphism was associated with increased risk for AD (mostly in synergy with the effect of APOE 4) [48,49,[54][55][56], risk of psychosis in AD [45,57,58], and higher alcohol consumption in AD [52]. Several studies showed no association between COMT Val158Met polymorphism and AD [59][60][61][62], while others showed that COMT Val158Met A allele is, in fact, associated with AD [63,64,7].…”

Section: Discussionmentioning

confidence: 99%

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Relationships of Cerebrospinal Fluid Alzheimer’s Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms

Leko

Perković

Klepac

et al. 2020

JAD

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The noradrenergic and dopaminergic systems are affected in Alzheimer's disease (AD). Polymorphisms in genes encoding enzymes and proteins that are components of these systems can affect products of transcription and translation and lead to altered enzymatic activity and alterations in overall dopamine and noradrenaline levels. Catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAOB) are the enzymes that regulate degradation of dopamine, while dopamine ␤hydroxylase (DBH) is involved in synthesis of noradrenaline. COMT Val158Met (rs4680), DBH rs1611115 (also called -1021C/T or -970C/T), and MAOB rs1799836 (also called A644G) polymorphisms have been previously associated with AD. We assessed whether these polymorphisms are associated with cerebrospinal fluid (CSF) AD biomarkers including total tau (t-tau), phosphorylated tau proteins (p-tau 181 , p-tau 199 , and p-tau 231 ), amyloid-␤ 42 (A␤ 42 ), and visinin-like protein 1 (VILIP-1) to test possible relationships of specific genotypes and pathological levels of CSF AD biomarkers. The study included 233 subjects: 115 AD, 53 mild cognitive impairment, 54 subjects with other primary causes of dementia, and 11 healthy controls. Significant decrease in A␤ 42 levels was found in patients with GG compared to AG COMT Val158Met genotype, while t-tau and p-tau 181 levels were increased in patients with AA compared to AG COMT Val158Met genotype. A␤ 42 levels were also decreased in carriers of A allele in MAO-B rs1799836 polymorphism, while p-tau 181 levels were increased in carriers of T allele in DBH rs1611115 polymorphism. These results indicate that COMT Val158Met, DBH rs1611115, and MAOB rs1799836 polymorphisms deserve further investigation as genetic markers of AD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relationships of Cerebrospinal Fluid Alzheimer’s Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms

Leko

Perković

Klepac

et al. 2020

JAD

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“…Late-onset AD is generally defined as 'sporadic', given the lack of specific genetic factors directly associated with the disease. Genome-wide association studies (GWAS) have shown that AD is also associated with variations of several gene loci, such as the apolipoprotein E 4 allele (APOE 4) [13][14][15][16][17]. Accumulation of amyloid-␤ (A␤) plaques and neurofibrillary tangles, composed of accumulated microtubule-associated total, and phosphorylated tau (t-tau and p-tau) protein, are the two physiological hallmarks of human AD, though it is unclear what role, if any, they play in the disease [18] (Supplementary Table 1).…”

Section: Ad and Inadequacy Of Traditional Ad Modelsmentioning

confidence: 99%

A Human-Based Integrated Framework forAlzheimer’s Disease Research

Pistollato

Cavanaugh

Chandrasekera

2015

JAD

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Abstract. Animal models of Alzheimer's disease (AD) have been extensively utilized for decades in an effort to elucidate the pathophysiological mechanisms of this disease and to test novel therapeutic approaches. However, research success has not effectively translated into therapeutic success for human patients. This translational failure is partially due to the overuse of animal models that cannot accurately recapitulate human AD etiopathogenesis or drug responses and the inadequate use of human-relevant research methods. Here, we propose how to mitigate this translational barrier by employing human-based methods to elucidate disease processes occurring at multiple levels of complexity, accounting for gene and protein expression and the impact of disease at the cellular, tissue/organ, individual, and population levels. In particular, novel human-based cellular and computational models, together with epidemiological and clinical studies, represent the ideal tools to facilitate human-relevant data acquisition, in the effort to better elucidate AD pathogenesis in a human-based setting and design more effective treatments and preventive strategies. Our analysis indicates that a paradigm shift toward human-based, rather than animal-based research is required in the face of the ever-increasing prevalence of AD in the 21st century.

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Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms

Sun

Cai

et al. 2021

Mutation Research/Reviews in Mutation Research

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Association between the catechol‐O‐methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population

Abstract: Although genetic association between the polymorphism and the onset of AD in a Japanese population were not observed, the polymorphism affected the risk for HAC-AD.

Cited by 5 publications

References 32 publications

Relationships of Cerebrospinal Fluid Alzheimer’s Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms

Relationships of Cerebrospinal Fluid Alzheimer’s Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms

A Human-Based Integrated Framework forAlzheimer’s Disease Research

Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms

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