Meta-analysis of MTHFR C677T and A1298C gene polymorphisms: Association with the risk of hepatocellular carcinoma

Qi, Yuhong; Yao, Liping; Cui, Guang-Bin; Liang, Jun; Shao, Qing; Yan, Ling-Feng; Du, Pang

doi:10.1016/j.clinre.2013.10.002

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…Upon comparison of 1500 cases of HCC, 1500 healthy controls and individuals with the wild-type homozygous genotype, Zhang H et al[73]indicated that genetic variants in OCM genes (including MTHFR ) may contribute to HCC susceptibility, as those with the heterozygous genotype had a higher HCC risk. Qi YH et al[74]reported that homozygous carriers of the MTHFR C677T mutation are more susceptible to HCC, but homozygous mutations of MTHFR A1298C may play a protective role in the development of HCC. More interestingly, the protective role of the MTHFR A1298C polymorphism is more obvious when the controls examined are healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

Liu

et al. 2017

PLoS ONE

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Background/AimsFolic acid (FA) is a core micronutrient involved in DNA synthesis/methylation, and the metabolism of FA is responsible for genomic stability. MicroRNAs may affect gene expression during folate metabolism when cellular homeostasis is changed. This study aimed to reveal the relationship between FA deficiency and the expression of miR-22-p/miR-149-5p and the targeted regulation of miR-22-3p/miR-149-5p on the key folate metabolic gene Methylenetetrahydrofolate reductase (MTHFR).MethodsNormal (HL-7702 cells) and cancerous (QGY-7703 cells) human hepatocytes were intervened in modified RPMI 1640 with FA deficiency for 21 days. The interaction between MTHFR and the tested miRNAs was verified by Dual-Luciferase Reporter Assays. The changes in the expression of miR-22-3p/miR-149-5p in response to FA deficiency were detected by Poly (A) Tailing RT-qPCR, and the expression of MTHFR at both the transcriptional and translational levels was determined by RT-qPCR and Western blotting, respectively.ResultMiR-22-3p/miR-149-5p directly targeted the 3’UTR sequence of the MTHFR gene. FA deficiency led to an upregulation of miR-22-3p/miR-149-5p expression in QGY-7703/HL-7702 cells, while the transcription of MTHFR was decreased in QGY-7703 cells but elevated in HL-7702 cells. Western blotting showed that FA deficiency resulted in a decline of the MTHFR protein in QGY-7703 cells, whereas in HL-7702 cells, the MTHFR protein level remained constant.ConclusionThe results suggested that miR-22-3p/miR-149-5p exert different post-transcriptional effects on MTHFR under conditions of FA deficiency in normal and cancerous human hepatocytes. The results also implied that miR-22-3p/miR-149-5p might exert anticancer effects in cases of long-term FA deficiency.

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Section: Discussionmentioning

confidence: 99%

Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

Liu

et al. 2017

PLoS ONE

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“…Additionally, a meta-analysis showed that the CC genotype of rs1881131 is a protective factor in patients with HCC (27) and other cancers (28).…”

Section: ' Discussionmentioning

confidence: 99%

Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

Carvalho¹,

Vasconcelos²,

Fonseca³

et al. 2021

Clinics

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The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0. ]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 ]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.

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“…Some pooled analysis investigated a potential correlation of MTHFR rs1801133 with HCC risk. Several meta-analyses reported that MTHFR rs1801133 A allele might increase the risk of HCC [31–33,38]. However, in another meta-analysis, Qin et al [30] suggested that there was no significant association between MTHFR rs1801133 locus and HCC risk.…”

Section: Discussionmentioning

confidence: 99%

Association between methylenetetrahydrofolate reductase tagging polymorphisms and susceptibility of hepatocellular carcinoma: a case–control study

et al. 2019

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Polymorphisms in one-carbon metabolism genes may influence the susceptibility to hepatocellular carcinoma (HCC). In the present study, we studied methylenetetrahydrofolate reductase (MTHFR) tagging polymorphisms in 584 HCC cases and 923 controls. Polymerase chain reaction was harnessed to detect MTHFR genotype. Overall, our results showed that genotype distribution of MTHFR rs4846048 and rs4845882 polymorphisms was not different between HCC patients and controls. MTHFR rs9651118 and rs1801133 loci were protective factors for HCC (rs9651118: CT vs. TT: adjusted odds ratio (OR) = 0.67, 95% confidence interval (CI): 0.49–0.90, P=0.008 and TC/CC vs. TT: adjusted OR = 0.70, 95% CI: 0.53–0.93, P=0.015; rs1801133: GA vs. GG: adjusted OR = 0.72, 95% CI: 0.54–0.97, P=0.031, AA/GA vs. GG: adjusted OR = 0.76, 95% CI: 0.57–0.99, P=0.045). However, MTHFR rs3753584 locus was a candidate for susceptibility to HCC (CT vs. TT: adjusted OR = 1.67, 95% CI: 1.20–2.32, P=0.003 and TC/CC vs. TT: adjusted OR = 1.59, 95% CI: 1.15–2.20, P=0.005). Results of haplotype analysis suggested that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Trs9651118 was associated with the risk of HCC (OR = 1.55, 95% CI: 1.16–2.07, P=0.003). The power of our study also confirmed these associations (the value of power >0.80). In summary, our findings suggested that MTHFR rs3753584, rs9651118 and rs1801133 polymorphisms may affect the risk of HCC in Chinese Han population. In future, our findings should be further validated in additional case–control studies.

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Meta-analysis of MTHFR C677T and A1298C gene polymorphisms: Association with the risk of hepatocellular carcinoma

Cited by 15 publications

References 27 publications

Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

Association between methylenetetrahydrofolate reductase tagging polymorphisms and susceptibility of hepatocellular carcinoma: a case–control study

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