Vitamin D Receptor Rs11568820 Research Articles

Vitamin D receptor rs3782905 and vitamin D binding protein rs7041 polymorphisms are associated with hepatocellular carcinoma susceptibility in cirrhotic HCV patients

BackgroundThe severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are associated with genetic variations within vitamin D receptor (VDR) in several populations. This study aims to determine the significance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection and their effect on the progression of liver cirrhosis to carcinogenesis.MethodsSingle nucleotide polymorphisms (SNPs) VDR (rs2228570, rs3782905), and DBP rs7041 were genotyped using restriction fragment length-PCR (RFLP-PCR) technique and VDR rs11568820 was genotyped using single strand polymorphism PCR (SSP PCR). 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).ResultThe VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly higher in HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are higher in 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.ConclusionAmong the four investigated SNPs, there are associations between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. These SNPs are considered as risk factors in HCV induced liver cirrhosis and HCC. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. Future research with a larger sample size of subjects with HCV infection is advised, because chronic liver disease induced by HCV infection is the primary cause of HCC in Egypt. We recommend screening of these SNPs for prediction of LC and HCC development in HCV infected patients, which may improve the used therapeutic protocol. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.

The Correlation Between Vitamin D Receptor (VDR) Gene Polymorphisms and Autism: A Meta-analysis.

Vitamin D receptor (VDR) polymorphisms are risk factors for autism. We performed a systematic meta-analysis to explore the relationship between VDR gene polymorphisms and autism. A literature review of articles from Pubmed, Embase, the Cochrane Library, and Springer was conducted up to January 28, 2019. The association between SNPs and autism was calculated using pooled odd ratios (ORs) and 95% confidence intervals (CIs). Additionally, tests for heterogeneity, publication bias, and sensitivity were conducted. Six eligible studies with a total of 2001 participants (1045 cases and 956 controls) were included. Meta-analysis indicated that the "C" allele of the rs731236 gene, including C vs. T (OR = 1.3254, 95% CI = 1.0897-1.6122), CC vs. TT (OR = 2.0871, 95% CI = 1.3395-3.2519), and CC vs. TT + CT (OR = 1.9610, 95% CI = 1.2985-2.9615), might be a risk factor for autism. Moreover, the "G" allele of rs7975232 (G vs. T: OR = 0.8228, 95% CI = 0.6814-0.9934) was associated with a protective effect against the development of autism. No significant differences were found in the allele frequencies of rs11568820, rs1544410, and rs2228570 in the cases and controls. This meta-analysis revealed that both VDR rs731236 and rs7975232 were significantly associated with autism, whereas VDR rs11568820, rs1544410, and rs2228570 might not be correlated with the incidence of autism.

Association of vitamin D receptor and Toll like receptor variants with colon cancer related risk: A case control study in Egypt

Variants of vitamin D receptor (VDR) and toll like receptors (TLR) have been investigated in relation to colon cancer (CC) susceptibility, however results were always inconsistent. MethodsWe examined the association of CC risk with four variants VDR rs2228570 (FokI), VDR rs11568820 (Cdx2) and Asp299Gly (rs4986790) and Asp399Ile (rs4986791) in TLR4. rs11568820 was assessed by allele specific-multiplex polymerase chain reaction, while the other variants were examined by restriction fragment length polymorphism. We evaluated whether any of the associations differed by tumor location or criteria. ResultsThe A allele of rs11568820 was associated with decreased risk with adjusted OR = 0.523 (0.344–0.796), p = 0.002, while G allele in Asp299Gly and T allele in Thr399Ile were associated with >3 fold increased risk of CC with OR = 3.430 (1.588–7.408), p = 0.002 and OR = 3.290 (1.628–6.648), p = 0.001 respectively. G allele of Asp299Gly was more strongly associated with distal tumors OR = 4.952 (2.171–11.29), p < 0.001 than proximal tumors OR = 2.401 (1.002–5.751), p = 0.043 with almost 2 fold rise in the OR. On the other hand rs11568820 A allele was more associated with proximal tumors OR = 0.574 (0.355–0.926), p = 0.022 than distal tumors OR = 0.400 (0.224–0.712), p = 0.001. ConclusionsWe conclude significant association of VDR rs11568820 (Cdx2) and TLR4 variants with CC, although results should be confirmed in additional studies.

Association of vitamin D receptor and toll like receptor genetic variants and haplotypes with colon cancer risk: A case control study in Egypt

Variants of vitamin D receptor (VDR) and toll like receptors (TLR) have been investigated in relation to colon cancer (CC) susceptibility, however results were always inconsistent. Methods: We examined the association of CC risk with four variants VDR rs2228570 (FokI), VDR rs11568820 (Cdx2) and Asp299Gly (rs4986790) and Asp399Ile (rs4986791) in TLR4. rs11568820 was assessed by allele specific-multiplex polymerase chain reaction, while the other variants were examined by restriction fragment length polymorphism. We evaluated whether any of the associations differed by tumor location or criteria. Results: The A allele of rs11568820 was associated with decreased risk with adjusted OR=0.523 (0.344–0.796), p=0.002, while G allele in Asp299Gly and T allele in Thr399Ile were associated with >3 fold increased risk of CC with OR=3.430 (1.588–7.408), p=0.002 and OR=3.290 (1.628–6.648), p=0.001 respectively. G allele of Asp299Gly was more strongly associated with distal tumors OR=4.952 (2.171–11.29), p<0.001 than proximal tumors OR=2.401 (1.002–5.751), p=0.043 with almost 2 fold rise in the OR. On the other hand rs11568820 A allele was more associated with proximal tumors OR=0.574 (0.355–0.926), p=0.022 than distal tumors OR=0.400 (0.224–0.712), p=0.001. Haplotype analysis showed that the VDR haplotype A-F was associated with decreased CC risk with adjusted OR=0.483 (0.309-0.753), p=0.001. While in TL4 varients, both haplotypes A-T and G-C were associated with increased CC risk with adjusted OR=3.705 (1.706-8.046), p=0.001 and 4.401 (1.690-9.663), p=0.002 respectively. ConclusionsWe conclude significant association of VDR rs11568820 (Cdx2) and TLR4 variants with CC, although results should be confirmed in additional studies.

Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population.

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.