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Association Of Vitamin D Receptor And Vitamin D Binding Protein Polymorphisms With Hepatitis B-related Liver Disease

Posted on:2015-03-13Degree:MasterType:Thesis
Country:ChinaCandidate:S YangFull Text:PDF
GTID:2254330431453070Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
Objectives To explore the vitamin D receptor (VDR) gene singlenucleotide polymorphism (SNP) of rs11568820, rs2228570, rs3782905, andvitamin D-binding protein (Vitamin D Binding Protein, DBP) gene SNP rs7041in Guangxi population and analyze the association between rs11568820,rs2228570, rs3782905,rs7041polymorphisms and hepatitis B (CHB), livercirrhosis (LC),hepatocellular carcinoma (HCC) in Guangxi, the objective of thisstudy is to provide new insight in the prevention and treatment of liver diseasewith HBV infection.Methods Polymerase chain reaction-restriction fragment lengthpolymorphism (PCR-RFLP) strategy, polymerase chain reaction-sequencespecific primers (PCR-SSP) strategy and DNA sequencing methods were used toanalyze polymorphysms of VDR and DBP in192patiens with CHB,104patientswith LC,184patients with HCC and180healthy controls. The SHEsis sofwarewas used to construct the haplotypes of VDR gene polymorphisms. The logisticregression analysis was used to calculate odds ration (OR) and95%confidenceinterval (95%CI) among different genotypes. Results1. The genotype distributions of VDR rs11568820, rs2228570, rs3782905,and DBP rs7041in four groups were consistent with HWE, the sample of ourstudy were representative and comparable.2. There were three genotypes in VDR rs11568820polymorphism (GG,GA and AA). The GA genotype was associated with reduced risk ofCHB(p=0.045,OR=0.637,95%CI:0.410-0.991). The A allele was associatedwith reduced the risk of CHB (p=0.037,OR=0.725,95%CI:0.536-0.980). Therewere three genotypes in VDR rs2228570polymorphism(CC,CT and TT).The TTgenotype was associated with increased risk of CHB and HCC(p=0.047,OR=1.792,95%CI:1.008-3.187;p=0.019,OR=2.149,95%CI:1.134-4.075).TheT allele was associated with increased risk of CHB and HCC(p=0.046,OR=1.342,95%CI:1.005-1.792;p=0.016,OR=1.489,95%CI:1.077-2.060).There were three genotypes in VDR rs3782905polymorphism(CC,CG andGG).The genetic polymophism of VDR rs3782905was not associated withsusceptibility to CHB,LC and HCC(p>0.05). There were three genotypes inDBP rs7041polymorphism(TT,TG and GG). The GG genotype was associatedwith increased risk of LC and HCC(p=0.002,OR=4.011,95%CI:1.676-9.603;p=0.026,OR=2.576,95%CI:1.121-5.921). The T allele was associated withincreased risk of LC and HCC(p=0.002,OR=4.011,95%CI:1.676-9.603;p=0.026,OR=2.576,95%CI:1.121-5.921).3. The genetic polymophisms of VDR rs11568820and rs3782905were notassociated with susceptibility to CHB, LC and HCC in males (p>0.05).The VDRrs2228570site CT genotype, TT genotype and T allele increase the risk of CHBand HCC in males. The DBP rs7041site GG genotype and G allele increase therisk of LC and HCC in males.4. In the female population, the three SNPs of VDR and one SNP of DBP were not associated with susceptibility to CHB, LC and HCC.5. Eight haplotypes of VDR SNPs were constructed in this study.GTChaplotypes increase the risk of CHB(p=0.014,OR=1.492,95%CI:1.085-2.054).6. The frequency distribution of genotype and allele for rs11568820,rs2228570, rs3782905and rs7041in Guangxi population were similar with theresults of yellows in Asia area, but was signigicantly different in whites andblacks.7. Compare the concentration of25-hydroxyvitamin D among CHB, LCand HCC. The serum25-hydroxyvitamin D levels were statistically significantdifferences (p <0.05) by CHB Group, LC and HCC increments.Comclusions1. The rs11568820polymorphism of GA genotype and A allele may beprotective factors for CHB. The rs2228570polymorphism of TT genotype and Tallele may be risk factors for CHB and HCC. The rs7041polymorphism of GGgenotype and G allele may be risk factors for LC and HCC.2. The rs2228570polymorphism of CT genotype, TT genotype and Tallele may be risk factors for CHB and HCC in males. The rs7041polymorphism of GG genotype and G allele may be risk factors for LC andHCC in males.3. Vitamin D may be involved in the development of hepatitis B-relatedliver disease. The levels increasing with the severity.
Keywords/Search Tags:vitamin D receptor, vitamin D binding protein, singlenucleotide polymorphism, chronic hepatitis B, liver cirrhosis, hepatocellular
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