Ming Yue

A novel polymorphism near HLA class II region is associated with spontaneous clearance of HCV and response to interferon treatment in Chinese patients

A recent genome-wide association study (GWAS) has identified the single-nucleotide polymorphism (SNP) rs4273729 in a 100-kbp region comprising human leukocyte antigens (HLAs) class II genes as an important predictor of hepatitis C virus (HCV) clearance in European and African populations. This study was to determine whether this polymorphism is also associated with spontaneous HCV clearance as well as response to interferon treatment in Chinese patients. Thus, 686 chronic HCV carriers, 432 individuals with spontaneous viral clearance and 243 patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment were genotyped. The rs4273729 GG genotype was strongly associated with spontaneous HCV clearance as well as better IFN/RBV treatment response compared with the GC/CC genotypes in Chinese Han population (additive model: odds ratio (OR)=0.62, 95% confidence interval (95% CI)=0.51–0.76; OR=0.58, 95% CI=0.38–0.88, respectively). Rs4273729, rs12980275, baseline HCV RNA and platelet level were independent predictors for sustained virological response (SVR). The area under the receiver-operating characteristic curve (AUC) was 0.578 when including rs4273729 alone, but the prediction value was improved significantly (AUC=0.733) when further including rs12980275, baseline viral load and baseline platelet level. In conclusion, the genetic variation of rs4273729 is associated with clearance of HCV in both the natural course and the treatment process in Chinese Han population.

Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population.

Vitamin D and vitamin D receptor (VDR) are involved in multiple immune-mediated disorders including chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between plasma vitamin D level, VDR genetic polymorphisms and risk of HCV infection susceptibility and chronicity. Seven single nucleotide polymorphisms (SNPs) in VDR gene were genotyped and plasma 25-hydroxyvitamin D [25(OH)D] levels were measured in a Han Chinese population of 898 HCV persistent infection cases, 558 spontaneous clearance subjects and 1136 uninfected controls with high risk of HCV infection. In this case-control study, the average plasma 25(OH)D level in persistent infection patients was significantly lower than that in spontaneous clearance cases (P=0.039) and controls (P=0.005). Logistic analyses indicated that rs7975232-C, rs2239185-T and rs11574129-T alleles were significantly associated with a decreased risk of HCV infection susceptibility (all PBonferroni<0.05, in additive/dominant models; Ptrend=9.000×10(-4), combined effects in a locus-dosage manner). The protective effects of three favorable alleles were more evident among males, females and subjects aged ≤50years (all P<0.05). Haplotype analyses suggested that compared with the most frequent haplotype Ars7975232Trs731236Crs11574129, CTT was correlated with a reduced risk of HCV infection susceptibility (P=2.200×10(-3)). These findings implied that low vitamin D levels might be associated with an increased risk for HCV infection and chronicity, and favorable VDR variants (rs7975232-C, rs2239185-T and rs11574129-T) might contribute to a decreased susceptibility to HCV infection in a high-risk Chinese population.

Genetic variations in vitamin D receptor were associated with the outcomes of hepatitis C virus infection among Chinese population

Vitamin D has been considered as an immune modulator, and exerted the effect through the vitamin D receptor (VDR). This study investigated the associations of single-nucleotide polymorphisms (SNPs) of VDR with the outcomes of Hepatitis C virus (HCV) infection. Three SNPs (rs2228570, rs757343 and rs739837) were genotyped by TaqMan assay among Chinese population, including 538 HCV spontaneous clearance subjects, 834 persistent infection subjects and 1030 uninfected subjects. Binary logistic analyses were used to control the effects of confounding factors. The results showed that subjects with the rs757343 A allele and rs739837 A allele had the significantly reduced risk of HCV susceptibility (all PBonferroni<0.05 in dominant/additive model). In the stratified analysis, the protection of rs757343 A allele and rs739837 A allele against HCV infection remained effective in some subgroups. In addition, patients carrying rs739837 CA genotype were less prone to develop persistent infection (PBonferroni=0.033) and such effect still work in several subgroups in the stratified analysis. Furthermore, haplotype analysis indicated that when compared with the most frequent GC haplotype, the haplotype carrying AA (odds ratio (OR)=0.66, 95% confidence interval (CI)=0.56–0.78) and GA (OR=0.64, 95% CI=0.47–0.85) suggested a protective effect. Our findings indicated that the polymorphisms of VDR are associated with the outcomes of HCV infection among Chinese population.

Hepatitis C virus infection and risk factors in the general population: a large community-based study in eastern China, 2011–2012

Limited information is available on the prevalence of hepatitis C virus (HCV) in the general population in China. A community-based epidemiological study was conducted in three counties in eastern China. A total of 149 175 individuals were investigated in 60 communities in three counties in Jiangsu province, eastern China, of whom 1175 subjects [0·79%, 95% confidence interval (CI) 0·74-0·83] were HCV antibody positive. The prevalence was low in children (0·09%, 95% CI 0·04-0·17), but increased progressively from adolescents (0·20%, 95% CI 0·15-0·28) to adults aged ⩾21 years (95% CI 0·15-1·64). Women had a higher prevalence of HCV infection than men in most age groups. In a multilevel regression analysis, age, sex, education, occupation, blood transfusion [odds ratio (OR) 2·91, 95% CI 1·09-5·37], invasive testing (OR 1·28, 95% CI 1·14-1·61), and dental therapy (OR 2·27, 95% CI 1·41-3·42) were associated with HCV infection. In conclusion, although the prevalence of HCV in this population was lower than reported from national levels, the total reservoir of infection is significant and warrants public health measures, such as health education to limit the magnitude of the problem.

Genetic variants in interferon-λ 4 influences HCV clearance in Chinese Han population

Recent many studies indicated a novel dinucleotide variant in ss469415590 (TT vs. ΔG) of interferon-λ 4 (IFNL4) gene strongly associated with hepatitis C virus clearance. To evaluate the impact and clinical usefulness of IFNL4 ss469415590 genotype on predicting both spontaneous HCV clearance and response to therapy in Chinese population, we genotyped 795 chronic HCV carriers, 460 subjects with HCV natural clearance and 362 patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment. IFNL4 ss469415590 variant genotypes significantly decreased host HCV clearance, both spontaneous (dominant model: ORu2009=u20090.50, 95% CIu2009=u20090.36–0.71) and IFN-α induced (dominant model: ORu2009=u20090.32, 95% CIu2009=u20090.18–0.56). Multivariate stepwise analysis indicated that ss469415590, rs12979860, the level of baseline HCV RNA and platelet were as independent predictors for sustained virological response (SVR). But the area under the ROC curve (AUC) was only 0.58 for ss469415590, and it was elevated to 0.71 by adding rs12979860, baseline HCV RNA and platelet in the prediction model of SVR. Therefore, these findings underscore that although genetic factors of host and pathogen were commonly important during HCV clearance, ss469415590 may be also a strongly predictive marker in the Chinese population.

Polymorphisms of chemokine receptor genes and clearance of hepatitis C virus infection in Chinese population

BACKGROUNDnChemokine genes play an essential role in both spontaneous clearance in acute infection and therapy of HCV. We investigated whether several CXC family-related genes associated with HCV spontaneous clearance and response to treatment.nnnMETHODSnThe current study genotyped four SNPs, respectively are CXCR6 rs2234358, CXCL12 rs1801157, CXCL9 rs10336, rs3733236 to assess their associations with HCV spontaneous clearance and response to treatment in a two stage study (668 chronic and 400 resolvers in discovery group, meanwhile 333 chronic and 199 resolver in replication group), and a treatment cohort of HCV with 282 patients.nnnRESULTSnWe found that the CXCR6 rs2234358 was associated with HCV spontaneous clearance in Chinese Han population (dominant model: adjusted OR=1.62, 95%CI: 1.30-2.01; additive model: adjusted OR=1.43, 95%CI: 1.20-1.70). Patients carrying GT/TT genotypes had increased sustained virological response compared with patients carrying the GG genotype (dominant model: adjusted OR=2.23, 95%CI: 1.26-3.95).nnnCONCLUSIONnThese results suggest that CXCR6 rs2234358 is associated with spontaneous clearance of HCV and response to IFN-α/RBV therapy, which may be identified as a predictive marker in Chinese Han population of HCV.

Lower Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Promotes the Proliferation and Migration of Endometrial Carcinoma

Background The incidence and death rates of endometrial cancer are alarmingly increasing. The diagnosis and treatment of endometrial cancer is crucial to decreasing mortality. Cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate (ATP)-binding cassette transporter family and plays an essential role in anion regulation and tissue homeostasis of various epithelia. This study explored the expression of CFTR in endometrial carcinoma and the role of CFTR in proliferation and migration of endometrial carcinoma cells. Material/Methods Immunohistochemistry and real-time (RT)-PCR were used to test the expression of CFTR in normal endometrium and endometrial carcinoma. CFTR inhibitor was used to restrain the expression of CFTR on the endometrial carcinoma, the effects on the proliferation and migration of endometrial carcinoma cells were also studied. RT-PCR was performed to test the expression of mir-125b after restraining CFTR. Proliferation and migration capability of endometrial carcinoma cells were detected after transfection of endometrial carcinoma cells with mir-125b mimic. Results Compared with cells from normal endometrium, the expression of CFTR was significantly upregulated in endometrial carcinoma cells. After adding CFTR(inh)172, the capability for proliferation and transfer of endometrial carcinoma cells was strengthened, the expression of mir-125b was reduced, and after transfection with mir-125b mimics entering the endometrial carcinoma cells, the ability of the proliferation and transfer of endometrial carcinoma cells was also reduced. Conclusions The high expression of CFTR in the endometrial carcinoma cells played a pivotal role in restraining the proliferation and transfer of endometrial carcinoma cells.

Genetic variations in NF-κB were associated with the susceptibility to hepatitis C virus infection among Chinese high-risk population

Polymorphisms within NF-κB pathway genes may be linked to hepatitis C virus (HCV) infection susceptibility and outcomes. We investigated the associations between single nucleotide polymorphisms (SNPs) in NF-κB and the susceptibility as well as resolution of HCV infection. A Chinese population, including 1125 uninfected control cases, 558 cases with spontaneous viral clearance and 898 cases with persistent HCV infection, was genotyped for four SNPs (rs11820062, rs230530, rs1056890 and rs3774963) using a TaqMan assay. Our logistic analyses indicate that the subjects carrying RelA rs11820062 A allele had a significantly increased risk of HCV susceptibility (PBonferroniu2009<u20090.003125 in a dominant or additive model). In stratified analysis, the increased risk associated with rs11820062 A allele on HCV susceptibility remained in some case subgroups. This study demonstrates that a genetic variant involved in the NF-κB pathway gene (rs11820062 A allele) is associated with an increased HCV susceptibility within a high-risk Chinese population.

Genetic variants in chemokine CC subfamily genes influence hepatitis C virus viral clearance

Chemokine genes may influence both hepatitis C virus (HCV) spontaneous clearance in acute infection and treatment response in chronic infection. We conducted this study to evaluate whether the genetic variants in several CC family genes influence HCV spontaneous clearance and treatment response. The current research genotyped eight SNPs, including CCR1 rs3733096, rs13096371, CCR5 rs746492, rs1800874, CCL3 rs1130371, CCL5 rs3817656, CCL8 rs1133763, CCL14 rs854625, to explore their associations with HCV spontaneous clearance and response to treatment in two populations. We identified that the CCR1 rs3733096 (dominant model: adjusted ORu2009=u20092.29, 95% CIu2009=u20091.49–3.53, additive model: adjusted ORu2009=u20092.21, 95% CIu2009=u20091.50–3.25) and CCL5 rs3817656 (dominant model: ORu2009=u20091.37, 95% CIu2009=u20091.10–1.70, additive model: ORu2009=u20091.33, 95% CIu2009=u20091.12–1.58) were associated with HCV spontaneous clearance in Chinese Han population, while we found no association with treatment response. Moreover, the expression quantitative trait loci (eQTL) analysis showed that the risk alleles of rs3817656 were significantly associated with downregulated expression of CCL5 in whole blood (Pu2009<u20090.001). The polymorphism of CCR1 rs3733096 and CCL5 rs3817656 are associated with spontaneous clearance of HCV in Chinese Han population.

Genetic variation on the NFKB1 genes associates with the outcomes of HCV infection among Chinese Han population

AIMnTo investigate whether nuclear factor-kappa B1 (NFKB1) gene polymorphisms are associated with the outcomes of hepatitis C virus (HCV) infection in a Chinese high-risk population.nnnMETHODSnIn this case-control study, 984 HCV-uninfected controls, 221 infected individuals with spontaneous HCV clearance, and 456 with persistent HCV infection were enrolled. Rs28362491 and rs72696119 were genotyped using the ABI TaqMan allelic discrimination assay. The functional annotation of the identified single nucleotide polymorphisms (SNPs) were further evaluated by bioinformatics analysis.nnnRESULTSnSignificant differences were observed among the three groups (Pu202f<u202f0.001) in terms of the frequency of rs28362491 SNP. In logistic regression analysis, rs28362491-ATTG deleted (D) was associated with a significantly increased risk of HCV infection compared to the major-type rs28362491-ATTG inserted (I) (dominant model: adjusted ORu202f=u202f1.332, 95% CIu202f=u202f1.059-1.674, Pu202f=u202f0.014; additive model: adjusted ORu202f=u202f1.181, 95% CIu202f=u202f1.021-1.367, Pu202f=u202f0.025), after adjusting for age, gender, and route of infection. Based on the in silico prediction, the RegulomeDB score for SNP rs28362491 was 3a, indicating that it can potentially regulate the transcription and expression of NFKB1 gene.nnnCONCLUSIONnNFKB1 rs28362491-D allele was functionally associated with the increased risk of susceptibility to HCV infection in the Chinese Han population.