Association of Single Nucleotide Polymorphisms in VDR and DBP Genes with HBV-Related Hepatocellular Carcinoma Risk in a Chinese Population

Abstract

BackgroundPolymorphisms of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (DBP) have been widely investigated because of the complex role played by vitamin D in cancer tumorogenesis. In this study, we investigated the association between VDR and DBP gene polymorphisms and HBV-related HCC risk in a Chinese population.MethodsStudy subjects were divided into three groups: 184 HBV patients with HCC, 296 HBV patients without HCC, and 180 healthy controls. The VDR rs2228570, and rs3782905 and the DBP rs7041 polymorphisms were genotyped using PCR-RFLP and the VDR rs11568820 polymorphism was genotyped by PCR-SSP, respectively. DNA sequencing was performed to validate the genotype results.ResultsWe found that there were significant differences in the genotype and allele frequencies of the VDR rs2228570 and DBP rs7041 polymorphisms between HBV patients with HCC and healthy controls. The rs2228570 T allele was associated with a significant increased HBV-related HCC risk as compared with the C allele. The rs2228570 TT and TT/TC genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type CC homozygote. Similarly, the rs7041 G allele was associated with a significant increased HBV-related HCC risk as compared with the T allele. The rs7041 GG and GG/TG genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type TT homozygote. However, we did not observe any significant effect of VDR rs11568820, and rs3782905 polymorphisms on HBV-related HCC risk in this population. In haplotype analysis, we also did not find any significant differences in haplotype frequencies of the VDR gene between HBV patients with HCC and the healthy controls.ConclusionsWe conclude that the VDR rs2228570 and DBP rs7041 polymorphisms may contribute to increased susceptibility to HBV-related HCC in the Chinese population. Due to the marginal significance, further large and well-designed studies in diverse ethnic populations are needed to confirm our results.

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

“…Moreover, it had been reported that the antiproliferative effects of vitamin D against HCC cells correlate with intracellular VDR level [44,51]. Also, it had been reported that polymorphism at FokI locus was associated with increased HCC susceptibility in Egyptian patients infected with chronic hepatitis B and had a significant role in the determination of its clinicopathological characteristics [48,26]. VDR gene SNPs (ApaI CC genotypes, CCA[bAt]-haplotype and Taq AA genotype) were also reported to be significantly associated with high hepatitis C virus load but not with antiviral (peginterferon plus ribavirin) response in chronic HCV Asian patients [52].…”

“…VDR gene polymorphisms have been described in several chronic liver diseases such as liver cirrhosis [21], autoimmune hepatitis [22], primary sclerosing cholangitis [23] and primary biliary cirrhosis [24]. Moreover, it has been reported that there is a significant association between polymorphisms of VDR gene and the occurrence of HCC in alcoholic liver cirrhosis in Caucasian subjects [25], in HBV-infected patients [26] and even in patients with chronic HCV [27]. However, the data in the literature describing the possible association between VDR gene polymorphisms and hepatocellular carcinoma (HCC) development are scarce and inconclusive especially in patients infected with HCV.…”

Association of vitamin D binding protein polymorphisms with response to therapy in Egyptian chronic hepatitis C patients

“…Vitamin D binding protein polymorphisms were associated with hepatocellular carcinoma in hepatitis B virus (HBV) patients but to date, there are no studies to assess its role in predicting response to HBV therapy, therefore further research is encouraged in that area [44]. Similarly, vitamin D binding protein polymorpshisms have been associated with insulin resistance in chronic hepatitis C (CHC) patients [45].…”

VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg‐positive chronic hepatitis B patients treated with pegylated interferon

“…Nine single nucleotide polymorphisms (SNPs) of three critical genes in vitamin D metabolic pathway were genotyped, including VDR (rs7975232/ ApaI , rs1544410/ BsmI , rs757343/ Tru9I , rs2228570/ FokI , rs731236/ TaqI ), VDBP (rs4588, rs7041), 1α‐hydroxylase (cytochrome P450, family 27, subfamily b, polypeptide 1, CYP27B1 ) (rs10877012, rs3782130) …”