Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients

Allah, Hany M M Abdel; Zahran, Walid E.; El‐Masry, Samir; El-Bendary, Mahmoud; Soliman, A.A.

doi:10.1007/s10238-021-00747-3

Cited by 6 publications

(3 citation statements)

References 53 publications

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“…Excessive cigarette smoking and heavy alcohol consumption are associated with low plasma folate concentration, and hyperhomocysteinemia among patients with chronic hepatitis C infection, which may accelerate the progression of liver fibrosis in hepatic patients and possibly lead to liver cancer [21,22]. MTHFR variant C667T has also been associated with an increased risk of invasive cervical cancer and premalignant lesions, which also indicate a possible role of MTHFR in viral infectionassociated cancers [23]. The purpose of this case-control study is to assess the existence of associations between the MTHFR C677T and A1298C polymorphisms and the risk of HCC.…”

Section: Introductionmentioning

confidence: 99%

Associations of methylene tetrahydrofolate reductase (MTHFR) polymorphism with hepatocellular carcinoma in Egyptian population

Abozeid,

Zaki,

Nagah

et al. 2024

Egypt Liver Journal

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Liver serves as a hub for key metabolic pathways such as folate cycle that provides one-carbon units for a network of metabolic reactions. Methylenetetrahydrofolate reductase (MTHFR) is a rate limiting enzyme in folate metabolism and thus it is vital for DNA methylation, synthesis and repair [1]. The objective of this study was to evaluate an eventual association between MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population.Blood samples from patients and controls from Mansoura university hospital were used after signed consent and approval from Medical ethical committee. The two genetic loci were designed for amplification and genotyped by using PCR–RFLP.Our results clarify that, the most important predictors for HCC are T/T genotype of variant C677T and C/C genotype of variant (A1298C) with odds ratio 3.28 and 2.99 respectively. Also, MTHFR variant C677T genotype C/C or T/T combined with MTHFR variant A1298C genotype C/C were associated with an increased risk of HCC, with the OR, 2.6 and 7 respectively. CT genotype of MTHFR variant C677T showed significant difference between HCC grades and C allele of variant C677T showed significant difference in BCLC stages of HCC.Our data indicates that, the two variants (C677T and A1298C) constitute a risk factor for the development of HCC and this could be attributed to the low activities of the enzyme MTHFR that disturb one carbon metabolism and subsequently, DNA synthesis, repair and methylation, thus cellular redox state, growth, and proliferation.

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Section: Introductionmentioning

confidence: 99%

Associations of methylene tetrahydrofolate reductase (MTHFR) polymorphism with hepatocellular carcinoma in Egyptian population

Abozeid,

Zaki,

Nagah

et al. 2024

Egypt Liver Journal

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“…An evaluation using liver biopsy usually shows hepatic steatosis and fibrosis as the most frequent histological changes [ 2 ]. Previous studies suggested HCV patients more easily to develop hepatic steatosis than those presenting with other liver diseases [ 3 , 4 ]. In turn, persistent hepatic steatosis increases the risk of hepatocellular carcinoma (HCC) [ 5 , 6 ], which highlights the need for early detection and clinical intervention.…”

Section: Introductionmentioning

confidence: 99%

Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis

Wang,

Cao,

Guo

et al. 2023

Lipids Health Dis

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Background Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C. Methods The database “Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM” were retrieved to identify the literature. The quality of the selected literature was evaluated using the “the Newcastle–Ottawa Scale” (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by “Cochran's Q and I2”, with I2 ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used “Funnel plots”, “Egger’s tests” and “Begg’s tests” to evaluate biases in the literature. Results The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467–29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger’s and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable. Conclusions Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.

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“…Excessive cigarette smoking and heavy alcohol consumption are associated with low plasma folate concentration, and hyperhomocysteinemia among patients with chronic hepatitis C infection, which may accelerate the progression of liver brosis in CHC and possibly lead to liver cancer [19] [20]. MTHFR variant C667T has also been associated with an increased risk of invasive cervical cancer and premalignant lesions, which also indicate a possible role of MTHFR in viral infection-associated cancers [21]. The purpose of this case-control study is to assess the existence of associations between the MTHFR C677T and A1298C polymorphisms and the risk of HCC.…”

Section: Introductionmentioning

confidence: 99%

Associations of Methylenetetrahydrofolate reductase (MTHFR) polymorphism with Hepatocellular carcinoma In Egyptian population.

Abozeid,

zaki,

nagah

et al. 2023

Preprint

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Liver serves as a hub for key metabolic pathways such as folate cycle that provides one-carbon units for a network of metabolic reactions. Methylenetetrahydrofolate reductase (MTHFR) is a rate limiting enzyme in folate metabolism and thus it is vital for DNA methylation, synthesis and repair. The objective of this study was to evaluate an eventual association between MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. Blood samples from patients and controls from Mansoura university hospital were used after signed consent and approvement from Medical ethical committee. The two genetic loci were designed for amplification and genotyped by using PCR-RFLP. Our results clarify that, the most important predictors for HCC are T/T genotype of variant C677T and C/C genotype of variant (A1298C) with odds ratio 39.756, and 2.012 respectively. Also, MTHFR variant C677T genotype C/C or T/T combined with MTHFR variant A1298C genotype C/C were associated with an increased risk of HCC, with the OR, 2.6 and 7 respectively. CT genotype of MTHFR variant C677T showed significant difference between HCC grades and C allele of variant C677T showed significant difference in BCLC stages of HCC. Our data indicates that, the two variants (C677T and A1298C) constitute a risk factor for the development of HCC and this could be attributed to the low activities of the enzyme MTHFR that disturb one carbon metabolism and subsequently, DNA synthesis, repair and Methylation, cellular redox state, growth, and proliferation.

show abstract

Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients

Cited by 6 publications

References 53 publications

Associations of methylene tetrahydrofolate reductase (MTHFR) polymorphism with hepatocellular carcinoma in Egyptian population

Associations of methylene tetrahydrofolate reductase (MTHFR) polymorphism with hepatocellular carcinoma in Egyptian population

Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis

Associations of Methylenetetrahydrofolate reductase (MTHFR) polymorphism with Hepatocellular carcinoma In Egyptian population.

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