MTHFR 677C/T and 1298A/C mutations and non-alcoholic fatty liver disease

Kasapoğlu, Benan; Türkay, Cansel; Yalcin, Kadir Serkan; Koşar, Ali; Bozkurt, Alper

doi:10.7861/clinmedicine.15-3-248

Cited by 17 publications

(15 citation statements)

References 23 publications

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“…Hyperhomocysteinemia considered a risk factor for liver disease by increased oxidative stress, activation of pro-inflammatory factors and altered intracellular lipid metabolism, could explain NAFLD association with MTHFR-Val, but was not equivocally demonstrated: it may not exist in Caucasians, and could characterize only subjects homozygous for the variant. [15] In the dominant model we applied, no such effect was seen, similar to neighboring populations [16]. The conflicting results could be related to folate status, as suggested in CVD.…”

Section: Discussionmentioning

confidence: 72%

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

Csép

Szigeti

Szalman

2018

Acta Medica Marisiensis

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Objective: Methylene-tetrahydrofolate reductase (MTHFR) is involved in adapting metabolism to environmental challenges by various mechanisms, including the control of gene expression by epigenetic and post-translational changes of transcription factors. Though a metabolic syndrome candidate gene, association studies of its common polymorphism rs1801133 (MTHFR-Ala222Val) remain inconclusive with important ethnic differences, and the effect on disease progression was not addressed. Methods: 307 middle-aged metabolic syndrome patients in a central Romanian hospital setting were investigated metabolically, and genotyped by PCR-RFLP. Disease progression was assessed by the age of onset of metabolic components, as well as development of non-alcoholic fatty liver disease and atherosclerotic complications. Results: The minor allele frequency of rs1801133 was 30.13%. Metabolic parameters showed no statistically significant differences according to genotype, but variant carriers developed dysglycemia and dyslipidemia earlier (53.28±10.8 vs 59.44±9.31 years, p<0.05 and 58.57±11.31 vs 64.72±10.6 years, p<0.1).While the polymorphism did not influence hepatic complications, an inverse association was found for manifest atherosclerosis (OR=0.49, p=0.006, 95%CI:0.29-0.81), which may be folate-status dependent, and needs further investigations. Simultaneous analysis with transcription factor polymorphisms (rs1801282, rs8192678) showed that the more protective genotypes were present the later metabolic disturbances developed, and in the presence of the other two variants the apparent protective cardiovascular effect disappeared. Conclusions: The common functional polymorphism rs1801133 may influence metabolic syndrome progression, the age of onset of components and development of atherosclerotic complications. Besides simple additive effects, complex mitigating and aggravating variant interactions may exist, and the protective or predisposing outcome may depend on modifiable environmental factors.

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Section: Discussionmentioning

confidence: 72%

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

Csép

Szigeti

Szalman

2018

Acta Medica Marisiensis

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“…So, the association between serum Hcy levels and the prevalence of NAFLD is inconclusive. At the same time, contradictory results regarding the potential correlation between the MTHFR 677CT gene polymorphism and NAFLD have been reported 14, 15, 16. Therefore, the first aim of the present study was to confirm the association between MTHFR 677CT gene polymorphism and the prevalence of NAFLD.…”

Section: Introductionmentioning

confidence: 77%

The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China

et al. 2019

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The methylenetetrahydrofolate reductase (MTHFR) genotypes 677CT and 677TT are associated with elevated serum homocysteine (Hcy) levels by means of lowering the activity of MTHFR, and the increase in serum Hcy may be linked to increased susceptibility to non-alcoholic fatty liver disease (NAFLD). However, there are contradictory reports of the relationship among the MTHFR 677CT gene polymorphism, Hcy, and NAFLD. Therefore, the aim of this study was to identify potential associations and interactions of either Hcy levels or the MTHFR 677CT gene polymorphism with the susceptibility to NAFLD in a Chinese population. The association between the MTHFR 677 CT gene polymorphism and Hcy levels was determined in 243 subjects with NAFLD and 388 healthy subjects without NAFLD using polymerase chain reaction-restriction fragment length polymorphism analysis and high-performance liquid chromatography. In subjects with NAFLD, there was no statistical difference in the genotypic and allelic frequencies of the MTHFR 677 CT gene polymorphism, while serum Hcy levels were significantly higher in subjects with NAFLD. Furthermore, these results strongly suggest that the MTHFR 677CT gene polymorphism and NAFLD have a potential synergistic effect on Hcy elevation, although the MTHFR 677CT gene polymorphism was not correlated with NAFLD in a Chinese population.

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“…The variants of MTHFR gene have been shown to be able to decrease the level of folate, the enzyme activity of MTHFR [32]. Kasapoglu B et al suggested that homozygote mutations of A1298C and MTHFR C677T are positively related to the elevated concentrations of serum Hcy in NAFLD patients [33]. …”

Section: Discussionmentioning

confidence: 99%

MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by Targeting Methylene Tetrahydrofolate Reductase (MTHFR)

Yang

2017

Med Sci Monit

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The objective of our study was to explore the effect of polymorphism in miR-149 on the pathogenesis of NAFLD.Material/MethodsReal-time PCR was performed to explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and luciferase assay were investigated to verify MTHFR was the target gene of miR-149. Finally, Western-blot analysis and real-time PCR were performed to confirm the control of MTHFR by miR-149.ResultsIn this study, we found that miR-149 was apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR in hepatocytes genotyped as TT treated with FFA was evidently downregulated compared to control. Whereas, FFA had no obvious effect on MTHFR level in hepatocytes genotyped as CC. We searched an online miRNA database and found that miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149 mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose-dependently increased the level of MTHFR. And in hepatocytes genotyped as CC treated with or without FFA exhibited a similar inhibition effect of miR-149 on expression of MTHFR.ConclusionsThe data suggested that the polymorphism in miR-149 played an important role in the development of NAFLD via altering the expression of miR-149 as well as its target, MTHFR.

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MTHFR 677C/T and 1298A/C mutations and non-alcoholic fatty liver disease

Cited by 17 publications

References 23 publications

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China

MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by Targeting Methylene Tetrahydrofolate Reductase (MTHFR)

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