Mutations in Homocysteine Metabolism Genes Increase Keratin <i>N</i>-Homocysteinylation and Damage in Mice

Borowczyk, Kamila; Wróblewski, Jacek; Suliburska, Joanna; Akahoshi, Noriyuki; Ishii, Isao; Jakubowski, Hieronim

doi:10.1155/2018/7570850

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…25 26 Consistently, CVDs are associated with Hcy-thiolactone and N-Hcy-protein, rather than t-Hcys, 27 and the Hcy-thiolactone/creatinine ratio is a significant predictor of acute myocardial infarction, independent of traditional risk factors and t-Hcy. 28 The serum paraoxonase (PON1) carried by high-density lipoprotein (HDL) protects blood proteins from N-homocysteinylation by hydrolysis of Hcy-thiolactone into Hcy. 29 PON1/HTase activity is associated with CAD risk.…”

Section: Introductionmentioning

confidence: 99%

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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Thromboembolic manifestations are relativement frequent in patients with intermediate/severe hyperhomocysteinemia (> 30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15- 30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice. Lowering homocysteine trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half cases and related to B12 and/or folate deficiency and Addisson/Biermer disease in 55% of these cases. In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for vitamin B deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the lowering homocysteine effect according to hyperhomocysteinemia categories at baseline.

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Section: Introductionmentioning

confidence: 99%

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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“…One of the important cellular methylation processes is when betaine is involved in the remethylation of homocysteine to eliminate toxic metabolites [43]. Homocysteine is generated by deamination of methionine and is a toxic sulphur-containing intermediate product, and has various consequences for cells, such as oxidative stress, mitochondrial dysfunction, increased cytosolic calcium and protein damage [44], which all contribute to apoptosis [45]. Homocysteine generates ROS and inhibits the expression of antioxidant enzymes which might potentiate the toxic effects of ROS [45].…”

Section: Betainementioning

confidence: 99%

Deleterious Effects of Heat Stress on Poultry Production: Unveiling the Benefits of Betaine and Polyphenols

Shakeri

2022

Poultry

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Managing and controlling environmental temperature conditions using practical strategies is crucial to avoid the negative impacts of high environmental temperature, improving poultry production and welfare. High environmental temperature is one of the significant factors challenging poultry production during hot seasons or in tropical areas causing heat stress (HS). The detrimental effects of HS on broilers range from reduced growth performance to impaired poultry meat quality. HS impairs physiological responses caused by alteration in blood parameters, which could lead to impaired product quality by reducing moisture content and altering the production of antioxidant enzymes resulting in increased oxidative stress. There has been a focus on the use of nutritional supplements as a cost effective HS amelioration strategy, such as betaine and polyphenols. Supplementing broiler chicken’s diets with polyphenols aims to enhance growth performance via reduced levels of oxidative stress in tissues under HS conditions. Furthermore, using betaine as an osmolyte aims to protect tissues during osmotic stress conditions. The current review reveals that betaine and polyphenols are essential under crucial conditions such as HS to protect tissues from oxidative damage.

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“…Our previous research has shown that carriers of FLG 2282del4 mutation, who were heterozygous for C677T polymorphism in the MTHFR gene (1p36.22, OMIM 607093), were 7 times as likely to develop ichthyosis as subjects with wild-type 677CC genotype [15]. It was also found that an elevated plasma homocysteine level impaired not only the metabolism of sulfur-containing amino acids, methionine, and cysteine, but also keratin molecules [16], [17], [18] that might exacerbate the effects of FLG null mutations. Every of single nucleotide polymorphisms (SNPs) of one-carbon metabolism genes -MTHFR C677T (rs1801133) and A1298C (rs1801131), MTR A2756G (rs1805087) and MTRR A66G (rs1801394) -are associated with plasma homocysteine level [19], [20].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Polymorphisms in One-carbon Metabolism Genes on Manifestation of Ichthyosis Vulgaris

Fedota

Sadovnychenko

Chorna

et al. 2021

Open Access Maced J Med Sci

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BACKGROUND: Ichthyosis vulgaris is the most common type of Mendelian disorders of cornification, caused by loss-of-function mutations in the gene encoding epidermal protein filaggrin (FLG), namely R501X and 2282del4. FLG 2282del4 mutation in heterozygotes is incompletely penetrant. Polymorphisms in one-carbon metabolism genes could be associated with clinical manifestation of ichthyosis vulgaris. AIM: The purpose of the present study was to analyze the effects of MTHFR, MTR and MTRR polymorphisms in patients with ichthyosis vulgaris. METHODS: 31 patients with ichthyosis vulgaris, 7 their FLG heterozygous relatives without symptoms of disorder, and 150 healthy controls were enrolled in study. FLG null mutations —R501X (rs61816761) and 2282del4 (rs558269137) — and one-carbon metabolism gene polymorphisms — MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), MTR A2756G (rs1805087) and MTRR A66G (rs1801394) — were analyzed by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: Among patients with ichthyosis, heterozygous for FLG 2282del4 mutation, the distributions of genotypes for folate metabolism genes were: MTHFR C677T CC:CT:TT —29.4%:70.6%:0.0%; MTHFR A1298C AA:AC:CC — 52.9%:47.1%:0.0%; MTR A2756G AA:AG:GG — 70.3%:23.5%:5.9%; MTRR A66G AA:AG:GG — 23.4%:52.9%:23.5%. The frequencies of MTR 2756AA and MTRR 66GG genotypes were 1.4–1.6 times higher in affected individuals heterozygous for 2282del4 than in patients with other FLG genotypes. In affected 2282del4 heterozygotes, the frequency of MTR 2756AA genotype was 1.6 times greater than in healthy controls (p<0.01). The strongest association was found between MTHFR 677CT/MTHFR 1298AA/MTR 2756AA/MTRR 66AG genotype and ichthyosis — OR=11.23 (95% CI 2.51−50.21, p=0.002). CONCLUSIONS: Various genotypes of one-carbon metabolism genes increase the risk of ichthyosis in heterozygotes for the FLG 2282del4 mutation (OR 2.799‑11.231). The most probable predisposing genotype is 677CT/1298AA/2756AA+AG/66AG.

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Mutations in Homocysteine Metabolism Genes Increase Keratin N-Homocysteinylation and Damage in Mice

Cited by 5 publications

References 23 publications

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Deleterious Effects of Heat Stress on Poultry Production: Unveiling the Benefits of Betaine and Polyphenols

The Effects of Polymorphisms in One-carbon Metabolism Genes on Manifestation of Ichthyosis Vulgaris

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