Genetic Polymorphism of MTHFR C677T Influences Susceptibility to HBV-Related Hepatocellular Carcinoma in a Chinese Population: a Case-Control Study

Qiao, Kunyan; Zhang, Shitian; Trieu, Congdoanh; Dai, Qinghai; Huo, Zhixiao; Du, Yanan; Lu, Wei; Hou, Wei

doi:10.7754/clin.lab.2016.161003

Cited by 9 publications

(5 citation statements)

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“…MTHFR C677T mutations are associated with reduced enzyme activity. The MTHFR C677T polymorphism with TT genotype may be a factor in the increased risk of HBV-associated HCC in the Chinese population, especially in individuals whose HBV infection has persisted for more than 20 years [ 48 ]. The folate level is mainly affected by the MTHFR C677T polymorphism.…”

Section: Folate and Liver Diseasesmentioning

confidence: 99%

Role of Folate in Liver Diseases

Yang,

Wang,

Wang

et al. 2024

Nutrients

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Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.

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Section: Folate and Liver Diseasesmentioning

confidence: 99%

Role of Folate in Liver Diseases

Yang,

Wang,

Wang

et al. 2024

Nutrients

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“…A total of nineteen articles were included and 6941 hepatocellular carcinoma patients and 9436 healthy controls were enrolled [13,29,[32][33][34][43][44][45][46][47][48][49][50][51][52][53][54][55][56] (The flow chat of literature selection was showed in Figure 1 and Table S1 (see Table S1, Supplemental Digital Content, which showed the flow chat of literature selection, http://links.lww.com/MD/G441). The characteristics of the included studies were showed in Table 1.…”

Section: The Characteristics Of the Included Studiesmentioning

confidence: 99%

“…Former meta-analyzes in 2014 and 2015 reported the MTHFR rs1801133 polymorphism was associated with an increased risk of HCC, but for the MTHFR rs1801131 polymorphism, no association was observed [30,31] . Since then, controversial results emerged in different regions and ethnicities [13,29,32–34] . In order to reach a more accurate evaluation of these 2 polymorphisms and HCC risk, we performed an update meta-analysis with trial sequential analysis.…”

Section: Introductionmentioning

confidence: 99%

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Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk

Wang¹,

Ma²,

Guo³

et al. 2021

Medicine

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“…Abnormal MTHFR function is related to an imbalance of DNA synthesis, methylation, and cellular replication as well as low folate status in the plasma/red blood cells, resulting in the accumulation of plasma homocysteine, further increasing oxidative stress (P53 oxidative lesions)/endothelial dysfunction. Reduced MTHFR activity is associated with a high-risk for the development of HCC and is correlated with a lower risk of late-stage HCC and favorable survival outcomes in patients with HCC [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-22-3p and MicroRNA-149-5p Inhibit Human Hepatocellular Carcinoma Cell Growth and Metastasis Properties by Regulating Methylenetetrahydrofolate Reductase

Wang

et al. 2022

CIMB

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microRNAs are small endogenous noncoding RNAs that have emerged as key negative regulators that target gene expression through RISC. Our previous study showed that the methylenetetrahydrofolate reductase gene (MTHFR) plays a key role in one carbon metabolism, which is downregulated by miR-22-3p and miR-149-5p, and that it could exert a potential anti-cancer effect. Whether miR-22-3p/miR-149-5p can regulate MTHFR to exert anti-cancer effects has become the focus of our research. Normal (HL-7702 cells) and cancerous (QGY-7703/HepG2 cells) human hepatocellular cells were transfected with 100 nM hsa-miR-22-3p/hsa-miR-149-5p mimic or controls. After 24, 48, and 72 h, cell proliferation ability was tested using CCK-8. The changes in MTHFR expression at both the transcriptional and translational levels were determined by RT-qPCR and Western blotting, respectively. Cancerous cell invasion and migration ability were confirmed by means of a transwell assay. We found that ectopic miR-22-3p/miR-149-5p inhibits hepatocellular carcinoma cell proliferation but does not inhibit normal human hepatocyte proliferation. The transfection of ectopic miR-22-3p/miR-149-5p downregulated the MTHFR expression in QGY-7703 and HepG2 but not in HL-7702. QGY-7703 and HepG2 migration and invasion were inhibited by ectopic miR-22-3p/miR-149-5p. Additionally, we found that ectopic miR-22-3p/miR-149-5p significantly increased the expression of TP53INP1 and PDCD4 in QGY-7703. The results of the study suggest that miRNA-22-3p and miRNA-149-5p inhibit tumor growth and metastasis properties may be by regulating MTHFR and that they exert anticancer effects in hepatocellular carcinoma cells.

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Genetic Polymorphism of MTHFR C677T Influences Susceptibility to HBV-Related Hepatocellular Carcinoma in a Chinese Population: a Case-Control Study

Abstract: MTHFR C677T polymorphism with TT genotype could be a factor that increases the risk of HBVrelated HCC in a Chinese population, especially those with HBV infection duration of more than 20 years.

Cited by 9 publications

References 0 publications

Role of Folate in Liver Diseases

Role of Folate in Liver Diseases

Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk

MicroRNA-22-3p and MicroRNA-149-5p Inhibit Human Hepatocellular Carcinoma Cell Growth and Metastasis Properties by Regulating Methylenetetrahydrofolate Reductase

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