Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population

Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF-alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty-three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case-control study in the Beijing area of China. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP-PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the -238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF-alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.     

Association of -238G／A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population

AIM: To clarify whether -238G/A polymorphism of tumor necrosis factor-a (TNF-a) gene promoter region was associated with outcomes of hepatitis B virus (HBV) infection in Han population of northern China, and to analyze the geneenvironment interaction between -238G/A polymorphism and cigarette smoking or alcohol consumption. METHODS: A case-control study was conducted to analyze the association of TNF-a gene promoter polymorphism with HBV infection outcomes. A total of 207 patients with chronic hepatitis B (HB) and 148 cases of self-limited HBV infection from Ditan Hospital and Shunyi District Hospital in Beijing, respectively were recruited. History of smoking and alcohol drinking was inquired by a questionnaire. The -238G/A polymorphism of TNF-a gene promoter was genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of GG and GA genotypes were 98.07% and 1.93% in chronic HB patients and 93.24% and 6.76% in self-limited HBV infection individuals, respectively (X^2=5.30, P=-0.02). The frequency of G allele was significantly higher in patients with chronic HB that in individuals with self-limited HBV infection (99.03% vs 96.62%, X^2=5.20, P=0.02). Only modestly increased risk of onset of chronic HB was found in smokers (OR=1.40, 95% CI： 0.87-2.28, P=0.14) and drinkers (OR=-1.26, 95%CI： 0.78-2.05, P=-0.32). There was a positive interaction between genotype GG and cigarette smoking with an interaction index (Ⅱ) of 2.95, or alcohol consumption with an Ⅱ of 1.64. CONCLUSION: The -238G/A polymorphism of TNF-a gene promoter region is independently associated with different outcomes of HBV infection.     

Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection.

OBJECTIVES: We evaluated the influence of tumor necrosis factor-alpha (TNF-alpha) promoter gene polymorphisms on clearance of hepatitis B virus (HBV) and outcome of HBV chronic hepatitis. METHODS: Four TNF-alpha promoter polymorphisms (T-1031C, C-863A, G-308A, and G-238A) were evaluated by direct sequencing in 184 chronic HBV carriers hepatitis B surface antigen (HBsAg) positive and 96 controls with documented sero-clearance (HBsAg negativity, positivity for anti-HBs and anti-HBc IgG). Frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in the control group were compared with those of the chronic carrier group and with clinically defined subgroups of the latter: asymptomatic carriers, patients with compensated hepatitis, decompensated cirrhotics, and patients with hepatocellular carcinoma. Furthermore, subgroups of chronic carriers were compared among them. Results: In the chronic carrier group, the -308 G allele was more frequent in those with a family history of HBV infection (96% vs 88% of those with non-familial transmission). The G/G genotype at position -308 was found in all chronic carriers with decompensated cirrhosis but in only 78% of controls (P=0.01) and was more frequent in decompensated cirrhotics than in the other subgroups. The distribution of TNF-alpha gene polymorphisms in the carrier group was not significantly different from that in the sero-clearance control group. TNF-alpha SNPs at positions -1031/-863 and -863/-238 were in linkage disequilibrium. The TCGG haplotype (-T1031, -C863, -G308, -G238) was significantly associated with end-stage liver disease. CONCLUSION: The TNF-alpha promoter polymorphisms do not appear to be determinant of HBV sero-clearance in southern Italians. The genotype -308G/G and haplotype TCGG are associated with an unfavorable prognosis in patients with chronic HBV infection.     

Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-alpha gene promoter polymorphisms

BACKGROUND: The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-alpha and interleukin(IL)-10 gene promoter. METHODS: A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 with chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (-1082, -819, -592), and TNF-alpha gene promoter (-308, -238) were assessed by single base primer extension assay. RESULTS: The frequency of C/C genotype at position -592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, P = 0.036). The IL-10 gene promoter -592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex (P = 0.003). Genotype frequencies of TNF-alpha gene promoter at position -308 and -238 were not different between the clearance and the persistence group in univariate analysis, but in multivariate analysis after adjusting for age and sex, -308G/-238G homozygotes were associated with HBV persistence (P = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease. CONCLUSIONS: The carriers of the -592A allele in the IL-10 promoter and -308G/-238G haplotype homozygotes in the TNF-alpha promoter region have higher risk of persistent HBV infection.     

血清IL-17水平及其基因多态性与HBV感染临床转归之间的关系研究*

目的 探讨血清白介素（IL）-17水平和IL-17-197A/G基因单核苷酸多态性与乙型肝炎病毒（HBV）感染临床转归之间的关系。方法 2015年3月~2017年8月在我院就诊的乙型肝炎肝硬化40例,慢性乙型肝炎120例,无症状慢性HBV携带者60例和自限性HBV感染者80例。采用酶联免疫吸附试验检测血清IL-17水平,使用全自动生化仪检测血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBIL）水平,采用多聚酶链反应结合荧光探针DNA扩增技术检测血清HBV DNA载量,使用单核苷酸检测试剂盒检测IL-17-197A/G基因单核苷酸多态性。结果 乙型肝炎肝硬化组血清IL-17水平显著高于慢性乙型肝炎组、无症状慢性HBV携带者组和自限性HBV感染组（F_3,296=102.8,P均<0.05）;慢性乙型肝炎组血清IL-17水平显著高于无症状慢性HBV携带者组和自限性HBV感染组（P均<0.05）;在乙型肝炎肝硬化组,血清高HBV DNA载量组（>1×10⁵ copies/mL）血清IL-7水平更高（t=5.1,P<0.05）,血清ALT>40 U/L组血清IL-7水平更高（t=10.7,P<0.05）;在慢性乙型肝炎组和乙型肝炎肝硬化组,血清AST>40 U/L组血清IL-7水平更高（t=24.5,P<0.05;t=22.4,P<0.05）,血清TBIL>20 μmol/L组血清IL-7水平更高（t=7.3,P<0.05;t=12.8,P<0.05）;肝硬化患者IL-17-197 AA、AG和GG基因型分别为75.0%、10.0%和15.0%,等位基因A分布频率为57.5%,G分布频率为42.5%,而慢性乙型肝炎患者则分别为25.8%、16.7%、57.5%和34.2%、65.8%,组间差异显著（P<0.05）,乙型肝炎肝硬化组以IL-17-197 AA基因型和A等位基因分布频率为主,慢性乙型肝炎组以GG基因型和G等位基因分布频率为主,HBV携带者组以AA基因型和A等位基因分布为主,自限性HBV感染者以GG基因型和G等位基因分布为主。结论 宿主免疫水平和遗传背景的相互作用决定了HBV感染的临床转归,IL-17在乙型肝炎病毒感染慢性化进程中发挥了重要作用。IL-17-197A/G位点的AA基因型和A等位基因可能是HBV易感的宿主基因,增加了HBV感染的不良转归。     

Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population

Considerable evidence suggests that host genetic factor play an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection in several ethic groups. Association study was performed included 150 chronic HBV patients, 100 resolved hepatitis B and 150 healthy individuals with similar ethic background. Interestingly, human leucocyte antigen (HLA)-DR13 show a strong association with the clearance of HBV [odds ratio (OR) = 0.04, 95% confidence interval (CI) = 0.00-0.26, corrected P-value (P(c)) = 0.0008] similar to reports from several ethic groups. TNF-alpha promoter polymorphisms (-863, -308 and -238) were also analysed. Only -863 C allele was found to be significantly decreased in chronic HBV patients compared with healthy control (P(c) = 0.03, OR = 0.54, 95% CI = 0.35-0.84 respectively). This -863C allele was not in linkage disequilibrium with HLA-DR13 suggesting that other genetic markers linked with -863C might influence clearance of chronic HBV infection in Thai. When stratified chronic HBV patients into patients without hepatocellular carcinoma (HCC) and with HCC, the -863 A allele was significantly increased in the HCC group compared to healthy control (P(c) = 0.003, OR = 2.61, 95% CI = 1.49-4.60). Haplotype analysis (-863/-308/-238) revealed that the homozygosity of the haplotype (CGG/CGG) was a protective marker for HCC (OR = 0.37, 95% CI = 0.17-0.79, P(c) = 0.02). One can propose that carriers of -863A genotype are associated with increased levels of TNF-alpha in the liver in response to HBV infection and induce hapatocyte damage that may finally lead to HCC development. Additional study is needed to validate these finding and to further explore the genetic pathogenesis of HBV infection.     

Host TNF-alpha-1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection

OBJECTIVES: This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphism (SNP) could determine clinical and histological outcomes after Helicobacter pylori infection. METHODS: A total of 524 dyspeptic patients, 424 with and 100 without H. pylori infection, were checked for TNF-alpha promoter SNP over the locus on -1031(T/C), -863(C/A), -857(C/T), -806(C/T), and -308(G/A) by sequence-specific oligonucleotide probe. Each patient received panendoscopy to take gastric biopsy to detect H. pylori infection and its related histology using the updated Sydney's system. Gastric TNF-alpha expressions were stained by immunohistochemistry. RESULTS: In H. pylori-infected patients, -1031C or -863A carriers of TNF-alpha promoter had more severe gastric neutrophil infiltration and TNF-alpha gastric staining than individuals with -1031TT or -863CC genotype, respectively (p<0.05). The multivariate logistic regression verified both -1031C and -863A carriers were independent risk factors to have duodenal ulcers and gastric ulcer without IM in the H. pylori-infected hosts (p<0.05). As compared to -863CC and -1031TT genotype combinations, the ulcer risk after H. pylori infection was 2.46 (95% CI: 1.32-4.59, p相似文献   

The association between cytokine gene polymorphisms and the outcomes of chronic HBV infection.

OBJECTIVE: To investigate whether the polymorphisms in TNF-alphagene, IL-10 gene and IL-6 gene were associated with the outcomes of chronic HBV infection. METHODS: The genotypes at the position -238 and -308 of TNF-alphagene, -1082, -819 and -592 of IL-10 gene, -174 of IL-6 gene in the promoter region were detected in 62 chronic hepatitis B patients, 60 asymptomatic carriers and 63 heath controls by polymerase chain reaction-sequence specific primer assay. RESULTS: The frequency of G/G genotype at the position -238 in the promoter region of TNF-alphagene increased significantly in hepatitis B patients, in comparison with that in controls (83.9% versus 66.7%, P<0.05), whereas the frequency of G/A genotype at the same position decreased significantly in hepatitis B patients comparing with that in controls (16.1% versus 33.3%, P<0.05). Between chronic hepatitis B patients, asymptomatic carriers and heath controls, the genotypes frequency at the position -308 of TNF-alphagene, -1082, -819 and -592 of IL-10 gene, -174 of IL-6 gene in the promoter region showed no significant differences (P>0.05). CONCLUSIONS: The presence of G/A genotype at the position -238 may contribute to virus elimination, whereas the presence of G/G genotype at the position -238 may lead to virus persistent infection. There were no association between IL-10 gene and IL-6 gene polymorphisms and chronic HBV infection.     

Tripartite Motif-Containing 22 Gene -364T/C Polymorphism Associated With Hepatitis B Virus Infection in Chinese Han Population

Background:

Hepatitis B virus (HBV) infection significantly contributes to the onset of liver disease and hepatocellular carcinoma. Understanding the pathogenesis of HBV infection susceptibility could help us to control HBV infection effectively.

Objectives:

This study investigated single nucleotide polymorphisms (SNPs) of the tripartite motif-containing 22 (TRIM22) gene associated with HBV infection outcome.

Patients and Methods:

A total of 765 Chinese Han subjects were enrolled: 293 patients were presented with chronic hepatitis B (CHB), 224 were asymptomatic HBV carriers, 248 had self-limited HBV infection, and all of them were recruited for TRIM22 SNPs genotyping. RING and SPRY domains of TRIM22 gene were DNA-sequenced, and HBV serum markers and HBV DNA were measured quantitatively in all subjects.

Results:

243 (31.76%) of 765 Chinese Han patients showed genetic variation in the TRIM22 gene. TRIM22 SNPs were mainly in RING area -364T/C site, accounting for 98.35% of the population. There were no significant differences (P > 0.05) in the RING domain -364T/C SNP and allele frequencies between patients with chronic hepatitis and asymptomatic HBV carriers. The CC genotype of TRIM22 gene RING domain -364T/C locus (rs10838543) was associated with chronic HBV infection (OR = 2.30, 95% CI = 1.24-3.97, P = 0.0012; OR = 2.26, 95% CI = 1.08-3.74, P = 0.002) and a mutant allele C carrier of the TRIM22 gene was associated with HBV chronic infection (OR = 1.97, 95% CI = 1.10-3.75, P = 0.0049; OR = 2.12, 95% CI = 1.17-3.89, P = 0.0038).

Conclusions:

TRIM22 gene RING domain -364T/C polymorphism is associated with chronic HBV infection in Chinese Han population.     

Polymorphisms of microsomal triglycedde transfer protein in different hepatitis B virus-infected patients

AIM: To identify the two polymorphisms of microsomal triglyceride transfer protein (MTP) gene in the Chinese population and to explore their correlation with both hepatitis B virus (HBV) self-limited infection and persistent infection.METHODS: A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection (195 subjects without familial history),matched with age and sex,from the Chinese Han population were enrolled in this study.Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction (PCR).RESULTS: The ratio of males to females was 2.13:1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years,respectively.None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium.There was a linkage disequilibrium between H297Q and -493G/T(D'=0.77).As the X2 test was used,the genotype distribution of MTP-493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history (X2=8.543,P=0.015 and X2=7.199,P=0.019).The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history (X2=6.212,P=0.013).The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection (OR: 0.59; 95% CI: 0.389-0.897).CONCLUSION: The polymorphism of the MTP gene,T allele at -493,may be involved in determining the HBV infection outcomes,of which the mechanism needs to be further investigated.     

Polymorphisms of microsomal triglyceride transfer protein in different hepatitis B virus-infected patients

AIM： To identify the two polymorphisms of microsomal triglyceride transfer protein （MTP） gene in the Chinese population and to explore their correlation with both hepatitis B virus （HBV） self-limited infection and persistent infection.
METHODS： A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection （195 subjects without familial history）, matched with age and sex, from the Chinese Han population were enrolled in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction （PCR）.
RESULTS： The ratio of males to females was 2.13：1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years, respectively. None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium. There was a linkage disequilibrium between H297Q and -493G/T （D＇ = 0.77）. As the χ^2 test was used, the genotype distribution of MTP-493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history （χ^2 = 8.543, P = 0.015 and χ^2 = 7.199, P = 0.019）. The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history （χ^2 = 6.212, P = 0.013）. The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection （OR： 0.59; 95% CI： 0.389-0.897）. CONCLUSION： The polymorphism of the MTP gene, T allele at -493, may be involved in determining the HBV infection outcomes, of which the mechanism needs to be further investigated.     

Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma

BACKGROUND & AIMS: The aim of this study was to investigate the influence of hepatitis B virus (HBV) genotypes on the clinical outcome of chronic childhood HBV infection and hepatocellular carcinoma (HCC). METHODS: A total of 460 HBV carrier children were followed-up for 15 years and 26 children with HBV-related HCC were recruited. HBV genotyping was examined at enrollment and the latest follow-up of these carrier children and at diagnosis in HCC children. Viral load was checked at enrollment for the carrier children. These carriers were grouped based on their initial hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) status. The HBeAg positive (+) group was divided further into an HBeAg(+/+) group and HBeAg(+/-) group, depending on whether spontaneous HBeAg seroconversion occurred during the follow-up period. RESULTS: Genotype B constituted 73%, 86%, and 76% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+) groups, respectively. Genotype C was found in 27%, 8%, and 6% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+) group, respectively. Genotype C carriers were more prevalent in the HBeAg(+/+) group than the other 2 groups (P = .01), and had a delayed HBeAg seroconversion compared with the genotype B carriers (P < .001). Changes of genotype during the follow-up period were rare (2.8%). In those with HCC, genotype B was also the major type (74%). There was no difference in the baseline viral load between genotypes B and C. CONCLUSIONS: Although HBV genotype B dominates in children with chronic HBV infection and HCC in Taiwan, genotype C delays HBeAg seroconversion in pediatric chronic HBV infection.     

江西乙型肝炎病毒基因型分布及其与临床的相关性

目的了解江西慢性乙型肝炎患者血清乙型肝炎病毒（HBV）基因型的分布情况及HBV基因型与临床的关系。方法选择HBV DNA阳性的慢性乙型肝炎患者血清150份,患者分别诊断为慢性HBV携带者、慢性肝炎轻度、中度、重度和慢性重型肝炎,每组30例,采用多对型特异性引物巢式PCR法检测HBV基因型。结果本组慢性乙型肝炎患者HBV基因分型结果为B型118例（78．7％）,C型31例（20．7％）,D型1例（0．6％）;在上述5组患者中C型比例分别为0％,16．7％,26．7％,30．0％和30．0％,其中慢性HBV携带者与其他组比,差异有统计学意义（P〈0．05）;B、C两基因型患者HBeAg阳性率分别为83．9％（99／118）和90．3％（28／31）,HBeAb阳性率分别为16．1％（19／118）和9．7％（3／31）,差异均无统计学意义（P〉0．05）。结论江西地区HBV优势基因型以B型为主,C型次之,有少量的D型感染者。     

The tumour necrosis factor-α-238A allele increases the risk of chronic HBV infection in European populations

Tumour necrosis factor-α (TNF-α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF-α genes. However, there have been conflicting results reported in previous studies on TNF-α-238 and TNF-α-863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966-August, 2010) and China Biological Medicine Database (January, 1978-August, 2010) and carried out a meta-analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta-analysis did not suggest significant associations of TNF-α-238 and TNF-α-863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF-α-238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07-4.58, P = 0.032; OR = 4.46, 95% CI: 1.75-11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF-α-238A allele may increase the risk of chronic HBV infection in European populations.     

Wild-type precore and core promoter sequences in patients with acute self-limited or chronic hepatitis B

BACKGROUND: Mutations in the precore region and core promoter were compared between patients with acute and chronic hepatitis B. METHODS: There were 69 patients with acute self-limited hepatitis B and 210 with chronic hepatitis B who had been followed for > 15 years. The hepatitis B virus (HBV) of genotypes A, B and C was detected in 14 (23%), 8 (13%) and 28 (45%) of the patients with acute self-limited hepatitis, respectively, in contrast to 11 (5%), 25 (12%) and 167 (80%) of those with chronic hepatitis. RESULTS: At presentation, hepatitis B e antigen (HBeAg) in serum was the more common (82% versus 65%, P < 0.05), and the wild-type sequences of the precore region (100% versus 74%, P < 0.001) and core promoter (88% versus 36%, P < 0.00001) were more frequent in the 50 patients with acute self-limited hepatitis than the 203 patients with chronic hepatitis B who were infected with HBV of genotype A, B or C. Wild-types of both the precore region and core promoter persisted in acute self-limited hepatitis, while they decreased from 28% to 10% in chronic hepatitis over the course of > 15 years. CONCLUSION: HBV with the wild-type sequences of the precore region and core promoter prevails in patients with acute self-limited hepatitis, unlike in patients with chronic hepatitis.     

Association of pre-S deletion mutant of hepatitis B virus with risk of hepatocellular carcinoma

BACKGROUND: Pre-S deletion mutant of hepatitis B virus (HBV) affects the expression of middle and small surface proteins, resulting in intracellular accumulation of large surface protein. The correlation between pre-S deletion mutant and risk of hepatocellular carcinoma (HCC) in hepatitis B virus carriers remains unclear. METHODS: Using molecular assays, pre-S deletion mutant of HBV were determined in 266 patients with chronic HBV genotype B or C infection. They included 202 asymptomatic carriers and 64 HCC patients. RESULTS: The overall prevalence of pre-S deletion mutant was 16.5%. Hepatocellular carcinoma (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.23-8.48, P = 0.02) and genotype C (OR, 3.19; 95%CI, 1.54-6.62, P = 0.002) were independently associated with the presence of pre-S deletion mutant. The prevalence of pre-S deletion mutant was comparable between HCC patients with genotype B and C infection. Nevertheless, in asymptomatic carriers, patients with genotype C infection were significantly associated with the presence of pre-S deletion mutant compared to those with genotype B infection (20.8% vs 7.2%, P = 0.007). Compared with age- and genotype B-matched asymptomatic carriers, young HCC patients (<50 years of age) had a significantly higher frequency of pre-S deletion (3.4% vs 20%, P = 0.04). CONCLUSIONS: Pre-S deletion mutant is more frequent in HBV carriers with genotype C infection, and those with pre-S deletion mutant may be associated with the development of HCC, irrespective of HBV genotype.     

Tumour necrosis factor-α-857T allele reduces the risk of hepatitis B virus infection in an Asian population

Tumour necrosis factor-α (TNF-α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF-α-857 polymorphism and chronic HBV infection have reported conflicting results. So a meta-analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966-March, 2011) and the China Biological Medicine Database (January, 1978-March, 2011) were searched using the keywords TNF-α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta-analysis. All fourteen studies focussed on an Asian population. The overall meta-analysis suggested that TNF-α-857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71-0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy-Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68-0.98, P = 0.043; OR = 0.77, 95% CI: 0.68-0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70-0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF-α-857T allele reduces the risk of chronic HBV infection in this Asian population.     

Tumour necrosis factor‐α promoter region polymorphisms affect the course of spontaneous HBsAg clearance

Background: This study aimed to investigate the roles of tumour necrosis factor‐α (TNF‐α) gene polymorphisms in the spontaneous clearance of HBsAg after a hepatitis B virus (HBV) infection. Methods: Polymorphisms in the TNF‐α (?1031 T to C, ?863 C to A, ?857 C to T, ?308 G to A and ?238 G to A transition) gene were evaluated in 274 chronic HBV‐infected patients and 194 patients with resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated from 77 (28%) of the 274 chronic HBV‐infected patients with negative HBeAg and positive antibody to HBeAg were stimulated with HBcAg. Data on TNF‐α genotypes and phenotypes in subjects with/without the A allele at the TNF‐α?863 promoter single nucleotide polymorphism (rs1800630) were compared. Results: The A allele in the ?863 promoter region of the TNF‐α gene was present in 154 (56.2%) chronic HBV‐infected patients and 87 (44.8%) patients who recovered from HBV infection (odds ratio 1.58; P<0.01). The TNF‐α?863 A allele genotype predicted lower TNF‐α production by PBMC after in vitro HBcAg stimulation (P<0.02). Conclusions: The A allele at the ?863 locus of the promoter region of the TNF‐α gene predicts lower HBcAg‐inducible TNF‐α secretion. It is also associated with chronicity of HBV infection.     

Clinical significance and evolution of core promoter and precore mutations in HBeAg-positive patients with HBV genotype B and C: a longitudinal study.

BACKGROUND/AIMS: The aims of this longitudinal study were to investigate whether the clinical outcome and evolution of core promoter and precore mutations were different during hepatitis B e antigen (HBeAg) seroconversion between hepatitis B virus (HBV) genotypes B and C in HBeAg-positive patients with chronic hepatitis B. PATIENTS AND METHODS: The core promoter and precore sequences were determined from serial sera of 156 HBeAg-positive patients with chronic HBV infection. RESULTS: In HBV genotype C, the T1762/A1764 mutant was detected earlier than the A1896 mutant, and the frequency was significantly higher than in HBV genotype Ba over the entire follow-up period. In HBV genotype Ba, A1896 was found earlier than the T1762/A1764 mutant, and the frequency was significantly higher than in genotype C only before HBeAg seroconversion, and the A1896 mutant played an important role in HBeAg seroconversion in HBV genotype Ba. In addition, the T1846 variant was an independent factor associated with HBeAg seroconversion. Furthermore, HBV genotype C was associated with the development of G or C1753 and T1766/A1768 mutations, and the reactivation of hepatitis after HBeAg seroconversion. Based on Cox's regression analysis, the significant risk factors of liver cirrhosis were older age at entry [hazard ratio (HR)=1.085, 95% confidence interval (CI)=1.036-1.136, P=0.001], alanine transaminase (ALT) >80 U/l (HR=3.48, 95% CI=1.37-8.86, P=0.009), and the T1762/A1764 mutant (HR=5.54, 95% CI=2.18-14.08, P<0.001). CONCLUSIONS: Our study showed that different HBV genotypes were associated with various mutations in the core promoter and precore regions during HBeAg seroconversion. T1762/A1764 mutation could be useful in predicting clinical outcomes in HBeAg-positive patients with HBV infection.     

肿瘤坏死因子-α基因多态性与乙型肝炎病毒宫内感染易感性的关系

目的 探讨肿瘤坏死因子-α(TNF-α)基因-238位点G／A单核苷酸多态性与乙型肝炎病毒(HBV)宫内感染易感性的关系。方法 应用实时荧光定量聚合酶链反应技术检测HBV标志物阳性母亲所生45例HBV宫内感染儿童(Ⅰ组)、85例宫内未感染儿童(Ⅱ组)和126例对照组儿童TNF-α基因-238位点G／A单核苷酸多态性。结果 HBV宫内感染组TNF-α基因-238位点A等位基因频率显著高于HBV宫内未感染组(X^2=6．797，P=0．009)和对照组(X^2=9．513，P=0．002)，HBV宫内未感染组和对照组之间差异无显著性(X^2=0．047，P=0．828)。结论 TNF-α基因启动子区-238位点A等位基因与HBV宫内感染易感性相关，可作为检测其遗传易感性的标志之一。