Vitamin D receptor gene polymorphisms and risk of hepatocellular carcinoma in hepatitis C-related liver cirrhosis

Galal, Ghada Moustafa; Abudeif, Ahmad; Ahmed, Nagwa S.; Fahmy, Nahed; Sheneef, Abeer; Ali, Elsayed Mostafa; Abdelaal, Usama M.; Mohammad, Ahmad M.

doi:10.1186/s43066-020-00067-3

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…Our results are consistent with a number of studies demonstrating that the ApaI aa genotype is associated with progressive liver disease or the development of HCC in CHC [ 18 , 42 - 45 ], and even claiming that it could serve as a genetic marker to predict the risk of HCC in this setting [ 43 ]. Mohammed et al showed that an advanced stage of liver cirrhosis, lower serum concentrations of cholecalciferol and the occurrence of HCC were more frequent in patients carrying the dominant (Aa/aa) allele of the ApaI SNP [ 44 ].…”

Section: Discussionsupporting

confidence: 92%

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection

Tsounis¹

2022

aog

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Background Vitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC). Methods A total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data. Results The cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression. Conclusions In patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants.

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Section: Discussionsupporting

confidence: 92%

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection

Tsounis¹

2022

aog

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“…HCC is also known to be more common in men, and numerous SNPs have been linked to a higher genetic susceptibility to the disease [43]. In this study, there was no signi cant association between VDR SNPs (rs2228570 and rs3782905) and smoking status in HCC risk, which agreed with Galal et al, [22]. However, the GG genotype of DBP (rs7041) SNP was signi cantly associated with disease progression with both groups (non-smokers and smokers).…”

Section: Discussionsupporting

confidence: 91%

“…Few VDR SNPs have been examined concerning HCC risk factors in the Egyptian population [22,23], and it is still unclear in Egyptian patients whether DBP SNPs could be a risk factor for chronic liver diseases. As a result, this study aims to determine the signi cance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Receptor BsmI and Vitamin D Binding Protein Polymorphisms associated with Hepatocellular Carcinoma Susceptibility in Cirrhotic HCV Patients

Elmasry

Medhat

El-Bendary

et al. 2023

Preprint

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Background: The severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are currently associated with specific genetic variations within vitamin D receptor (VDR). This study aims to assess the association of VDR and vitamin D binding protein (DBP) gene polymorphisms with HCC susceptibility in Egyptian cirrhotic HCV patients. Methods: Single nucleotide polymorphisms (SNPs) in the VDR (rs2228570, rs3782905, rs11568820) and DBP rs7041 genes were genotyped using single-stranded polymorphism PCR (SSP-PCR) or restriction fragment length-PCR (RFLP-PCR) techniques. These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls). Logestic regression analysis was also applied to determine association with HCC progression risk. Result: The VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly correlated with a higher risk of HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are more associated with higher risk of HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported. Conclusion: Among the four investigated SNPs, there is an association between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.

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“…Although the relationship between HCV and HCC is well established, it is still unclear and poorly understood how directly HCV causes cancer. The interaction between environmental, viral, and host cofactors may result in multiple genetic alterations which gradually accumulate in hepatocytes leading to the development of HCC [ 3 ]. It is well known that metabolic derangements, such as adipokine imbalance, are associated with the development of cancer, including HCC [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

The role of serum visfatin and vaspin in hepatocellular carcinoma in hepatitis C-related liver cirrhosis

Abdelhamed,

Morsy,

Hefny

et al. 2023

ceh

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Aim of the study To investigate the role of the novel adipokines visfatin and vaspin in hepatitis C virus (HCV)-cirrhotic patients with and without hepatocellular carcinoma (HCC) and their association with tumour characteristics and liver dysfunction. Material and methods This case-control study was carried out between March 2021 and September 2021. Serum visfatin and vaspin were measured in 67 HCV-cirrhotic patients (37 had HCC, and 30 did not) and 20 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results Serum visfatin and vaspin were substantially elevated in HCC patients compared to those without HCC and healthy controls ( p = 0.001, < 0.0001, respectively) and significantly associated with hepatic dysfunction. At a cut-off value of 12.1 ng/ml, the sensitivity and specificity of the serum visfatin in detecting HCC were 67.6% and 83.3%, respectively. Serum vaspin at a cut-off value of 321 ng/dl had a sensitivity of 94.6% and specificity of 66.7%. In multivariate regression analysis, serum vaspin and albumin were independent risk factors for HCC development. Patients with Barcelona Clinic Liver Cancer (BCLC) stage D had significantly the highest serum levels of visfatin and vaspin ( p = 0.03, 0.008, respectively). Conclusions Serum visfatin and vaspin were substantially higher in HCC patients, associated with tumour stage, and might be considered as potential biomarkers of HCC, but this should be confirmed in larger independent cohorts of patients with liver cirrhosis. Serum vaspin and albumin were independent risk factors for HCC development. There was a substantial association between visfatin, vaspin, and the severity of the underlying liver dysfunction.

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Vitamin D receptor gene polymorphisms and risk of hepatocellular carcinoma in hepatitis C-related liver cirrhosis

Cited by 5 publications

References 28 publications

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection

Vitamin D Receptor BsmI and Vitamin D Binding Protein Polymorphisms associated with Hepatocellular Carcinoma Susceptibility in Cirrhotic HCV Patients

The role of serum visfatin and vaspin in hepatocellular carcinoma in hepatitis C-related liver cirrhosis

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