The Significance of Vitamin D Receptor Gene Polymorphisms for Susceptibility to Hepatocellular Carcinoma in Subjects Infected with Hepatitis C Virus

Mohammed, Mohammed Amin

doi:10.15406/ghoa.2017.07.00246

Cited by 6 publications

(11 citation statements)

References 59 publications

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“…We acknowledge certain limitations of the current study. First, the sample size was relatively small, which reduced the statistical power of the study; nevertheless, our results are consistent with previous data showing an association between VDR polymorphisms and the development of HCV-related liver complications [ 18 , 42 - 44 ]. Moreover, accurate assessment of fibrosis status in non-cirrhotic patients to further evaluate the role of VDR in intermediate stages of CHC would require liver biopsies, which were not available in all our patients.…”

Section: Discussionsupporting

confidence: 90%

“…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 ]. Consistent with this, Baur et al showed that fibrosis progression and cirrhosis, as estimated by histologic scoring methods, were correlated with the presence of the aa genotype, and also demonstrated an additive negative effect of low vitamin D and [CCA] haplotype with respect to liver disease worsening [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

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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: 90%

Section: Discussionmentioning

confidence: 99%

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

Tsounis¹

2022

aog

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“…This suggests that individuals who have this high IL-10 producer G allele or GG genotype are more susceptible to chronic HCV infection, whereas the presence of the A allele or -1082 AG genotype confers protection (19,39). Although serum levels of IL-10 were elevated in patients with G allele, we failed to show any significant variation in IL-10 -1082 GG genotype distribution between healthy controls and HCV-infected patients as also demonstrated by others (27).…”

Section: Factors Associated With Hcc Developmentsupporting

confidence: 65%

“…The presence of liver cirrhosis was ascertained by the occurrence of ascites, esophageal varices and/or bleeding, splenomegaly, jaundice, and imaging. HCC was diagnosed by four-phase multidetector computed tomography scan and dynamic contrastenhanced magnetic resonance imaging as mentioned elsewhere (27). Ninety-six patients had liver cirrhosis and 60 had HCC.…”

Section: Patientsmentioning

confidence: 99%

IL-10 Polymorphisms and Haplotypes Predict Susceptibility to Hepatocellular Carcinoma Occurrence in Patients with Hepatitis C Virus Infection from Northeast India

et al. 2020

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Chronic hepatitis C virus (HCV) infection leads to variable outcomes, ranging from prolonged slow hepatic damage leading to cirrhosis, and hepatocellular carcinoma (HCC). Polymorphism in cytokines IL-10 and IL-12 that impact the immune response to HCV infection may play a role in determining this outcome. This study was aimed to determine if polymorphisms in IL-10 and IL-12B contribute to HCV susceptibility and the risk of developing HCC in patients from Northeast India. IL-10 -1082, -819, -592 polymorphisms and IL-12B -1188 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism in a total of 266 HCV-infected patients and 100 age-and sex-matched controls. In the HCV-infected subjects, 110 patients had chronic hepatitis C (CHC), 96 with liver cirrhosis, and 60 with HCC. Serum levels of IL-10 were also measured and correlated with disease severity. Haplotype analysis for IL-10 polymorphisms was carried out. Statistical data were analyzed using SPSS ver. 22.0. The frequency of IL-10 -592 AA genotype/A allele was significantly higher in HCC patients than in CHC patients. The intermediate IL-10-producing ACC haplotype was significantly more frequent in HCC and cirrhotic patients than in CHC patients. No significant association was found for IL-10 -819, -592 and IL-12B -1188 polymorphisms with the susceptibility to HCV infection or occurrence of HCC in HCV-infected patients. IL-10 -592 CA polymorphism and IL-10 ACC haplotype are significant biomarkers of HCC in HCV-infected patients from Northeast India. Higher serum levels of IL-10 were also linked to higher disease severity.

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“…Thirty-five cycles of amplification were performed in a thermal cycler (T Gradient -Biometra). After the initial denaturation of DNA at 95 °C for 2 min, each cycle consisted of a denaturation step at 94 °C for 45 s, optimization of the primer annealing step modified to be at 58 °C for 1 min, an extension step at 72 °C for 1 min, and a final extension step at 72 °C for 7 min following the last cycle [15]. PCR products were analyzed on 2% agarose gel stained with ethidium bromide.…”

Section: Detection Of Vdr Polymorphisms Pcr (Polymerase Chain Reaction)mentioning

confidence: 99%

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

Galal

Abudeif

Ahmed

et al. 2021

Egypt Liver Journal

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Background HCV is a major risk factor for HCC; however, the exact mechanism of hepatocarcinogenesis is still not fully understood. Host genetic factors have been reported to play a significant role. Experimental studies support the tumor inhibitory effect of vitamin D on HCC cells. Several single nucleotide polymorphisms (SNPs) have been depicted in the vitamin D receptor (VDR) gene. We aimed to assess whether any of these polymorphisms could be significantly associated with increased risk of HCC. Results This study was conducted on 76 patients with HCV-related liver cirrhosis (48 patients had HCC on top of cirrhosis, and the other 28 had liver cirrhosis only). All patients underwent full medical history assessment, clinical examination, laboratory investigations, abdominal ultrasonography, and genotyping of the VDR gene. HCC patients had a significantly higher frequency of ApaI CC genotype compared with those patients without HCC. There is no statistically significant difference between the studied groups at any TaqI genotypes, but the carriage of the ApaI CC genotype had a significant association with liver disease severity in both patients groups compared with ApaI CA/AA genotypes. The carriage of the ApaI CC genotype was an independent predictor for HCC in HCV-related liver cirrhosis. Conclusions VDR ApaI polymorphism is significantly associated with the development of HCC; thus, ApaI CC genotype could be used as an important molecular marker to predict the risk of HCC in patients with HCV-related liver cirrhosis.

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The Significance of Vitamin D Receptor Gene Polymorphisms for Susceptibility to Hepatocellular Carcinoma in Subjects Infected with Hepatitis C Virus

Cited by 6 publications

References 59 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

IL-10 Polymorphisms and Haplotypes Predict Susceptibility to Hepatocellular Carcinoma Occurrence in Patients with Hepatitis C Virus Infection from Northeast India

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

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