Association of the transcobalamin II gene 776C→G polymorphism with Alzheimer’s type dementia: dependence on the 5, 10-methylenetetrahydrofolate reductase 1298A→C polymorphism genotype

Cascalheira, José F.; Gonçalves, Mónica; Barroso, Madalena; Castro, Rita; Palmeira, Manuela; Serpa, André; Dias-Cabral, A.C.; Domingues, Fernanda; Almeida, Sofia

doi:10.1177/0004563214561770

Cited by 11 publications

(8 citation statements)

References 35 publications

(76 reference statements)

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“…The results obtained in the present study, support the link between adenosine and methyl group metabolism, which is relevant since impairment of methyl group metabolism is a risk factor for several brain pathologies, including Alzheimer's Disease and glioblastoma (Cascalheira et al, , ; Semmler et al, ). Previous studies have shown that adenosine can regulate cell functions by interfering with the transmethylation pathway.…”

Section: Discussionsupporting

confidence: 84%

“…A recent study has shown that adenosine induces DNA hypomethylation in the brain through inhibition of transmethylation reactions (Williams‐Karnesky et al, ). This link between adenosine and methyl group metabolism is relevant since impairment of methyl group metabolism is a risk factor for several brain pathologies, including Alzheimer Disease and glioblastoma (Cascalheira et al, , ; Semmler, Simon, Moskau, & Linnebank, ).…”

Section: Introductionmentioning

confidence: 99%

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Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation

Marcelino

Nogueira

Santos

et al. 2019

Journal of Neurochemistry

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are Co-senior authors. Abbreviations Used:: ABT 702, 4-Amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl)pyrido[2,3-d]pyrimidine; ADA, adenosine deaminase; ADK, adenosine kinase; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; HA, Human astrocytes; ITU, 5-iodotubercidin; LDH, lactate dehydrogenase; AbstractBrain adenosine concentrations can reach micromolar concentrations in stressful situations such as stroke, neurodegenerative diseases or hypoxic regions of brain tumours. Adenosine can act by receptor-independent mechanism by reversing the reaction catalysed by S-adenosylhomocysteine (SAH) hydrolase, leading to SAH accumulation and inhibition of S-adenosylmethionine (SAM)-dependent methyl-

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation

Marcelino

Nogueira

Santos

et al. 2019

Journal of Neurochemistry

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“…Polymorphisms in the genes encoding for MTHFR (methylenetetrahydrofolate reductase) [162] and MTHFD1L (methylenetetrahydrofolate dehydrogenase [NADP + dependent] 1–like protein) [163] negatively influence key enzymes involved in the metabolism of homocysteine to form methionine. Similarly, polymorphisms in the gene encoding for an important carrier of vitamin B 12 in the circulation (transcobalamin II) are suggested to have a protective role against AD and are found to be occurring less often in patients with AD [164] . These polymorphisms provide a genetic basis for the long observed elevated homocysteine levels in AD indicative for compromised one-carbon metabolism and suggestive for higher requirements for vitamin B 12 and folate.…”

Section: Discussionmentioning

confidence: 99%

Lower brain and blood nutrient status in Alzheimer's disease: Results from meta‐analyses

Wilde

Vellas

Girault

et al. 2017

A&D Transl Res & Clin Interv

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IntroductionAlzheimer's disease (AD) patients are at risk of nutritional insufficiencies because of physiological and psychological factors. Recently, we showed the results of the meta-analyses indicating lower plasma levels of vitamins A, B12, C, E, and folate in AD patients compared with cognitively intact elderly controls (controls). Now, additional and more extensive literature searches were performed selecting studies which compare blood and brain/cerebrospinal fluid (CSF) levels of vitamins, minerals, trace elements, micronutrients, and fatty acids in AD patients versus controls.MethodsThe literature published after 1980 in Cochrane Central Register of Controlled Trials, Medline, and Embase electronic databases was systematically analyzed using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines to detect studies meeting the selection criteria. Search terms used are as follows: AD patients, Controls, vitamins, minerals, trace elements, micronutrients, and fatty acids. Random-effects meta-analyses using a linear mixed model with correction for age differences between AD patients and controls were performed when four or more publications were retrieved for a specific nutrient.ResultsRandom-effects meta-analyses of 116 selected publications showed significant lower CSF/brain levels of docosahexaenoic acid (DHA), choline-containing lipids, folate, vitamin B12, vitamin C, and vitamin E. In addition, AD patients showed lower circulatory levels of DHA, eicosapentaenoic acid, choline as phosphatidylcholine, and selenium.ConclusionThe current data show that patients with AD have lower CSF/brain availability of DHA, choline, vitamin B12, folate, vitamin C, and vitamin E. Directionally, brain nutrient status appears to parallel the lower circulatory nutrient status; however, more studies are required measuring simultaneously circulatory and central nutrient status to obtain better insight in this observation. The brain is dependent on nutrient supply from the circulation, which in combination with nutrient involvement in AD-pathophysiological mechanisms suggests that patients with AD may have specific nutritional requirements. This hypothesis could be tested using a multicomponent nutritional intervention.

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“…Cellular deficiency of Cbl caused by TCN2 can occur via three mechanisms: a lack of TCN2 to bind Cbl, the absence of immunoreactive TCN2, and non-functional TCN2 binding to Cbl [22]. TCN2 is reported to be associated with various diseases, including omphaloceles [23], Alzheimer's disease [24], and stroke [25]. Additionally, we have reported on the association of TCN2 and TCblR polymorphisms with RSA in a previous study [10].…”

Section: Introductionmentioning

confidence: 85%

Genetic polymorphisms of the cobalamin transport system are associated with idiopathic recurrent implantation failure

Park

Kim

et al. 2019

J Assist Reprod Genet

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Purpose Vitamin B12 (cobalamin, Cbl) plays a role in the recycling of folate, which is important in pregnancy. Transcobalamin II (TCN2) and transcobalamin receptor (TCblR) proteins are involved in the cellular uptake of Cbl. TCN2 binds Cbl in the plasma, and TCblR binds TCN2-Cbl at the cell surface. Therefore, we investigated the potential association between polymorphisms in Cbl transport proteins, TCN2 and TCblR, and recurrent implantation failure (RIF) susceptibility. Methods The genotypes of TCN2 67A>G, TCN2 776C>G, and TCblR 1104C>T were determined for RIF patients and healthy controls using a polymerase chain reaction restriction fragment length polymorphism assay. Additionally, statistical analysis was performed to compare the genotype frequencies between RIF patients and controls. Results The TCN2 67 polymorphism AG type was associated with RIF risk. Some allele combinations that contained the TCN2 67 polymorphism G allele were associated with increased RIF risk, whereas other allele combinations that contained the TCblR 1104 polymorphism T alleles were associated with decreased RIF risk. In genotype combination analysis, two combinations containing the TCN2 67 polymorphism AG type were associated with RIF risk. Conclusion Our study showed that the polymorphisms of TCN2 and TCblR are associated with RIF and are potential genetic predisposing factors for RIF among Korean women. Additionally, our findings support a potential role for TCN2 and TCblR in RIF among Korean women. However, further studies are required to investigate the role of the polymorphisms in those proteins and RIF because the roles of the TCN2 and TCblR polymorphisms in RIF are not clear.

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Association of the transcobalamin II gene 776C→G polymorphism with Alzheimer’s type dementia: dependence on the 5, 10-methylenetetrahydrofolate reductase 1298A→C polymorphism genotype

Abstract: The TCN2 776C → G polymorphism is negatively associated with Alzheimer's type dementia, suggesting a protective role against the disease in subjects with the 5, 10-methylenetetrahydrofolate reductase 1298AA genotype.

Cited by 11 publications

References 35 publications

Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation

Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation

Lower brain and blood nutrient status in Alzheimer's disease: Results from meta‐analyses

Genetic polymorphisms of the cobalamin transport system are associated with idiopathic recurrent implantation failure

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