ADAR1 up-regulates ZNF655 expression via RNA editing and enhances HBV replication in HepG2 cell line / 基础医学与临床

Objective To explore the effect of ADAR1 on ZNF655 and the regulation of ZNF655 on the expression of HBV. Methods Sanger sequencing was used to validate the 3′UTR region of ZNF655 in ADAR1. The expression of ADAR1 and ZNF655 mRNA as well as HBV RNA were detected by RT-qPCR. Dual luciferase report plasmid assay was used to detect the expression of luciferase. To detect the expression of ADAR1 and ZNF655 pro-tein by Western blot. HBsAg and HBeAg was detected by ELISA. Results The chr7:99575277 loci on ZNF655 3′UTR was homozygous in DNA level and hybrid in RNA level. On the 3′UTR editing site of ZNF655,the luciferase activity of the edited G allele was significantly higher than that of the normal A allele (P＜0.001). The expression of ZNF655 was upregulated by ADAR1 in the level of transcription and translation(P＜0.01).ZNF655 significantly promoted the expression of HBV. Conclusions The chr7:99575277 loci on ZNF655 3′UTR is edited by ADAR1, promoting the expression of ZNF655,which upregulated the expression of HBV.

Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKAL1, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.</p><p><b>METHODS</b>Twelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rs1111875 in HHEX, rs391300 in SRR, rs17584499 in PTPRD, rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.</p><p><b>RESULTS</b>Birthweight was inversely associated with CDKAL1-rs10946398 (β = -41 g [95% confidence interval [CI]: -80, -3], P = 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β = -36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction of birthweight (P = 0.085).</p><p><b>CONCLUSIONS</b>This study identified the association between type 2 diabetes risk variants in CDKAL1 and birthweight in Chinese Han individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.</p>

Study on association between vitamin D receptor gene polymorphisms and the outcomes of HBV infection / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore whether the vitamin D receptor gene (VDR) polymorphisms are associated with the outcomes of hepatitis B virus (HBV) infection in Chinese Han population.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of Fok I locus in exon 2 and Taq I locus in exon 9 of VDR gene. One hundred and eighty-four chronic hepatitis B patients and 205 asymptomatic HBV carriers were recruited to make the comparison of frequencies of genotype and haplotype of the VDR gene between the patients and the carriers.</p><p><b>RESULTS</b>The univariate analysis showed a significant difference in Fok I polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group. The FF genotype frequency in chronic hepatitis B patients group was 44.6%,higher than 31.7% in asymptomatic HBV carriers group (P<0.05). After adjusting the confounders by multiple logistic regression analysis, the result still showed a significant difference in Fok I site polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group (OR=1.95, P<0.05). The FT haplotype frequency in chronic hepatitis B patients group was higher than that in asymptomatic HBV carriers group (OR=1.45, P<0.05). The fT haplotype frequency in chronic hepatitis B patients group was lower than that in asymptomatic HBV carriers group (OR=0.72, P<0.05).</p><p><b>CONCLUSION</b>VDR gene polymorphism may be an influence factor of genetic susceptibility to HBV infection.</p>

Association of haplotype formed on HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of haplotype of HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection in Han population of north China.</p><p><b>METHODS</b>Two hundred and seven chronic hepatitis B (HB) patients, two hundred and twelve chronic asymptomatic hepatitis B virus (HBV) carriers (HBV carrier) and one hundred and forty-eight self-limited HBV infection were investigated for HLA-DRB1 and HLA-DQA1 alleles by sequence specific-polymerase chain reaction (PCR-SSP).</p><p><b>RESULTS</b>The frequency of DRB1*04-DQA1*0301 haplotype was 10.03% in self-limited HBV infection subjects, significantly higher than that in chronic HB patients (3.66%) (P=0.0005)ûthe frequency of DRB1*15/*16-DQA1*0102 haplotype was 6.80% in self-limited HBV infection subjects, significantly higher than 1.94% in chronic HB patients (P=0.0012) and 1.65% in asymptomatic HBV carriers (P=0.0004)ûwhile the frequency of DRB1*04-DQA1*0302 haplotype was 3.10% in chronic HB patients, higher than that in self-limited HBV infection subjects (0.39%) (P=0.0077).</p><p><b>CONCLUSION</b>Individuals with different haplotypes composed of HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.</p>

Association of polymorphisms of human leucocyte antigen -DRB1 and -DQA1 allele with outcomes of hepatitis B virus infection in Han population of north China / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess the association of polymorphisms of human leucocyte antigen (HLA) -DRB1 and -DQA1 region allele with outcomes of hepatitis B virus (HBV) infection in Han population of north China.</p><p><b>METHODS</b>A total of 207 chronic hepatitis B (HB) patients, 212 chronic asymptomatic HBV carriers (HBV carrier), and 148 self-limited HBV infection were recruited to examine the association between gene polymorphisms and outcomes of HBV infection. Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to genotype HLA-DRB1 and HLA-DQA1 loci.</p><p><b>RESULTS</b>The frequency of HLA-DQA1 * 0301 in chronic HB patients (14.81%) was significantly lower than those in HBV carriers (25.24%) and self-limited HBV infection subjects (25.00%) (Pc = 0.002; Pc = 0.007). The frequency of HLA-DQA1 * 0102 in self-limited HBV infection subjects (8.78%) was significantly higher than those in chronic HB patients (2.18%) and HBV carriers (1.89%) (Pc = 0.000; P = 0.000). In addition, the frequency of HLA-DQA1 * 0302 in self-limited HBV infection subjects (4.05%) was significantly lower than that in chronic HB patients (11.41%) (Pc = 0.005). HLA-DQA1 * 0302 was demonstrated to be risk factors of chronic HBV (OR = 3.913, P = 0.0006), while HLA-DQA1* 0102 and HLA-DQA1 * 0301 to be protective factors against chronic HBV (OR = 0.200, P = 0.0004; OR = 0.258, P = 0.0000) after age, sex, smoking and drinking were adjusted by logistic regression analysis. There were positive interactions between drinking and HLA-DQA1 * 0102 [interaction index (II) = 1.49] or HLA-DQA1 * 0302 (II = 12.12). There were negative interactions between drinking and HLA-DQA1 * 0301 (II = 0.78)</p><p><b>CONCLUSIONS</b>The subjects with HLA-DQA1 * 0302 allele have an increased risk to chronic HB infection compared with other subjects without this allele, while HLA-DQA1 * 0301 and HLA-DQA1 * 0102 are associated with HBV clearness. Gene-environment interaction can affect the outcomes of HBV infection.</p>

Association of TNFA polymorphisms with the outcomes of HBV infection / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore whether the TNFA promoter single nucleotide polymorphisms (SNPs) are associated with the outcomes of hepatitis B virus(HBV) infection in Chinese Han population.</p><p><b>METHODS</b>One hundred and forty-eight self-limited HBV infection subjects and 207 chronic hepatitis B patients were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific primer-PCR(PCR-SSP) were used to detect the SNPs of five sites in TNFA promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in different groups were analyzed by EPI and EH programs.</p><p><b>RESULTS</b>The frequencies of -238GG genotype in chronic hepatitis B patients were significantly higher than that in self-limited infection subjects (P=0.02). The frequencies of -857TT genotype in chronic hepatitis B patients were clearly lower than that in self-limited infection subjects (P=0.02). Haplotypic frequencies of GGCCT (-238/-308/-857/-863/-1031) in chronic hepatitis B patients was significantly lower than that in self-limited infection subjects (P=0.03), and the frequencies of haplotype GGCAT or GGTAT in chronic hepatitis B patients were clearly higher than those in self-limited infection subjects (P=0.0001; P=0.004).</p><p><b>CONCLUSION</b>TNFA promoter polymorphisms are important host genetic factors affecting the outcomes of HBV infection.</p>