Plasma Homocysteine Concentration is Associated with the Expression Level of Folate Receptor 3

Yoshitomi, Ren; Nakayama, Kai; Yamashita, Shigeki; Kumazoe, Motofumi; Lin, Ting Hsiang; Mei, Chen Yi; Marugame, Yuki; Fujimura, Yoshinori; Maeda‐Yamamoto, Mari; Kuriyama, Shinichi; Tachibana, Hirofumi

doi:10.1038/s41598-020-67288-9

Cited by 21 publications

(20 citation statements)

References 31 publications

(23 reference statements)

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“…HCys serum concentrations beyond 15 µmoL/L (≈2030 ng/mL) were considered high and referred to as hyperhomocysteinemia [ 74 ]. By feeding a diet deficient in vitamin B6, B12 and folate, we induced elevated levels of HCys beyond 15 µmoL/L and therefore, a hyperhomocysteinemic state in our mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Nieraad

Bruin

Arne

et al. 2021

IJMS

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Hyperhomocysteinemia has been suggested potentially to contribute to a variety of pathologies, such as Alzheimer’s disease (AD). While the impact of hyperhomocysteinemia on AD has been investigated extensively, there are scarce data on the effect of AD on hyperhomocysteinemia. The aim of this in vivo study was to investigate the kinetics of homocysteine (HCys) and homocysteic acid (HCA) and effects of AD-like pathology on the endogenous levels. The mice received a B-vitamin deficient diet for eight weeks, followed by the return to a balanced control diet for another eight weeks. Serum, urine, and brain tissues of AppNL-G-F knock-in and C57BL/6J wild type mice were analyzed for HCys and HCA using LC-MS/MS methods. Hyperhomocysteinemic levels were found in wild type and knock-in mice due to the consumption of the deficient diet for eight weeks, followed by a rapid normalization of the levels after the return to control chow. Hyperhomocysteinemic AppNL-G-F mice had significantly higher HCys in all matrices, but not HCA, compared to wild type control. Higher serum concentrations were associated with elevated levels in both the brain and in urine. Our findings confirm a significant impact of AD-like pathology on hyperhomocysteinemia in the AppNL-G-F mouse model. The immediate normalization of HCys and HCA after the supply of B-vitamins strengthens the idea of a B-vitamin intervention as a potentially preventive treatment option for HCys-related disorders such as AD.

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Section: Discussionmentioning

confidence: 99%

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Nieraad

Bruin

Arne

et al. 2021

IJMS

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“…1 Hcy metabolism. Abbreviations: blue-colored words, enzymes; green-colored words, cofactors (HHcy) [9]. Furthermore, the range of Hcy between 16 and 30 μmol/L is classified as moderate, 31-100 μmol/L as intermediate, and above 100 μmol/L as severe HHcy [6].…”

Section: Physiologic Hcy Levels and Severity Of Deviations: What Is The Most Optimal Hcy Concentration In Blood?mentioning

confidence: 99%

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

et al. 2021

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Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

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“…Several possible explanations have been proposed to offer some mechanistic insights. Hyperhomocysteinemia has been proposed as being part of the pathophysiology of cardiovascular disease due to its various biological effects, such as vascular damage, oxidative stress-induced DNA damage [ 32 ], neuronal apoptosis [ 33 ], cell cytotoxicity [ 34 ], and endothelial nitric oxide production [ 35 ]. Homocysteine acts as a methyl donor when it is converted to S-adenosyl-methionine, and a recent study demonstrated an association between the Hcy and DNA methylation in cardiovascular disease and dementia [ 36 , 37 ] with MTHFR C677T polymorphism, which suggests that Hcy also might play a role in the pathogenesis of those diseases via alterations in DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

The Homocysteine and Metabolic Syndrome: A Mendelian Randomization Study

Lee

Park

2021

Nutrients

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Homocysteine (Hcy) is well known to be increased in the metabolic syndrome (MetS) incidence. However, it remains unclear whether the relationship is causal or not. Recently, Mendelian Randomization (MR) has been popularly used to assess the causal influence. In this study, we adopted MR to investigate the causal influence of Hcy on MetS in adults using three independent cohorts. We considered one-sample MR and two-sample MR. We analyzed one-sample MR in 5902 individuals (2090 MetS cases and 3812 controls) from the KARE and two-sample MR from the HEXA (676 cases and 3017 controls) and CAVAS (1052 cases and 764 controls) datasets to evaluate whether genetically increased Hcy level influences the risk of MetS. In observation studies, the odds of MetS increased with higher Hcy concentrations (odds ratio (OR) 1.17, 95%CI 1.12–1.22, p < 0.01). One-sample MR was performed using two-stage least-squares regression, with an MTHFR C677T and weighted Hcy generic risk score as an instrument. Two-sample MR was performed with five genetic variants (rs12567136, rs1801133, rs2336377, rs1624230, and rs1836883) by GWAS data as the instrumental variables. For sensitivity analysis, weighted median and MR–Egger regression were used. Using one-sample MR, we found an increased risk of MetS (OR 2.07 per 1-SD Hcy increase). Two-sample MR supported that increased Hcy was significantly associated with increased MetS risk by using the inverse variance weighted (IVW) method (beta 0.723, SE 0.119, and p < 0.001), the weighted median regression method (beta 0.734, SE 0.097, and p < 0.001), and the MR–Egger method (beta 2.073, SE 0.843, and p = 0.014) in meta-analysis. The MR–Egger slope showed no evidence of pleiotropic effects (intercept −0.097, p = 0.107). In conclusion, this study represented the MR approach and elucidates the significant relationship between Hcy and the risk of MetS in the Korean population.

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Plasma Homocysteine Concentration is Associated with the Expression Level of Folate Receptor 3

Cited by 21 publications

References 31 publications

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person

The Homocysteine and Metabolic Syndrome: A Mendelian Randomization Study

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