Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virusrelated hepatocellular carcinoma

AIM to determine the relationship between five A3 G gene single nucleotide polymorphisms and the incidence of hepatitis B virus(HBV) infection and hepatocellular carcinoma(HCC). METHODS this association study was designed as a retrospective study, including 657 patients with chronic HBV infection(CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at the First Hospital of Jilin University(Changchun) were further classified into HBV-related HCC patients(n = 287) and non-HCC patients(n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNAwas extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.RESULTS there were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3 G gene polymorphisms, and risk of CHB and HBV-related HCC. the AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB(OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC(OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, tt genotypes and increased risk of HCC(OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.CONCLUSION this study indicates that the A3 G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.     

Mannose-binding lectin 2 rs11003123 polymor-phism is associated with the development of hepatocellular carcinoma in patients with hepa-titis B-related cirrhosis in the Chinese population

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associ-ated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population.
METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40).
RESULTS: We found that Child-Pugh proifles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A signiifcant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95%CI: 0.15-0.76;P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80;P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant geno-types (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85;P=0.004). However, no statistically signiifcant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 andP=0.384, respectively).
CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.     

HLA-DPB1 Variant Effect on Hepatitis B Virus Clearance and Liver Cirrhosis Development Among Southwest Chinese Population

Background:

Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.

Objectives:

We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.

Materials and Methods:

Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.

Results:

There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).

Conclusions:

Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.     

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

AIMTo investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODSWe enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.RESULTSThe PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed.CONCLUSIONIL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.     

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM: To examine the effect of interleukin-1-beta (IL-1beta) promoter region C-511T and IL-1 receptor antagonist (IL-1RN) polymorphism among the patients with chronic hepatitis B virus (HBV) infection (HCC and non-HCC). METHODS: Genomic DNA from 136 Thai patients with chronic HBV infection (HCC=46 and non-HCC=90) and 152 healthy individuals was genotyped for IL-1beta gene polymorphism (-511) using polymerase chain reaction with sequence specific primers (PCR-SSP). The variable number of tandem repeats (VNTR) of IL-1RN gene was assessed by a PCR-based assay. The association between these genes and status of the disease was evaluated by chi2 test. RESULTS: IL-1B-511 genotype C/C was found to be significantly different in patients with HCC when compared with healthy individuals (P=0.036, OR=2.29, 95%CI=1.05-4.97) and patients without HCC (P=0.036, OR=2.52, 95%CI=1.05-6.04). Analysis of allele frequencies of IL-1B-511 showed that IL-1B-511 C allele was also significantly increased in patients with HCC, compared to that in healthy control (P=0.033, OR=1.72, 95%CI=1.04-2.84). However, no significant association in IL-1RN gene was found between the two groups. CONCLUSION: IL-1B-511C allele, which may be associated with high IL-1B production in the liver, is a genetic marker for the development of HCC in chronic hepatitis B patients in Thai population.     

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

AIM To investigate possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV) infection and progression of liver diseases among clinically classified Vietnamese patients.METHODS Four IFR5 SNPs(rs13242262 A/T, rs77416878 C/T, rs10488630 A/G, and rs2280714 T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B(CHB). n = 99; liver cirrhosis(LC), n = 131; hepatocellular carcinoma(HCC), n = 149] and in 242 healthy controls by direct sequencing and Taq Man realtime PCR assays. RESULTS Comparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262 T and rs10488630 G contributed to an increased risk of liver cirrhosis(LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients(OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups(LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin. CONCLUSION Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.     

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM: To examine the effect of interleukin-1-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist (IL-1RN) polymorphism among the patients with chronic hepatitis B virus (HBV) infection (HCC and non-HCC).METHODS: Genomic DNA from 136 Thai patients with chronic HBV infection (HCC=46 and non-HCC=90) and 152 healthy individuals was genotyped for IL-1β gene polymorphism (-511) using polymerase chain reaction with sequence specific primers (PCR-SSP). The variable number of tandem repeats (VNTR) of IL-1RN gene was assessed by a PCR-based assay. The association between these genes and status of the disease was evaluated by X2 test.RESULTS: IL-1B-511 genotype C/C was found to be significantly different in patients with HCC when compared with healthy individuals (P = 0.036, OR = 2.29,95%CI = 1.05-4.97) and patients without HCC (P=0.036,OR=2.52, 95%CI=1.05-6.04). Analysis of allele frequencies of IL-1B-511 showed that IL-1B-511 C allele was also significantly increased in patients with HCC, compared to that in healthy control (P=0.033,OR= 1.72, 95%CI=1.04-2.84). However, no significant association in IL-1RN gene was found between the two groups.CONCLUSION: IL-1B-511C allele, which may be associated with high IL-1B production in the liver, is a genetic marker for the development of HCC in chronic hepatitis B patients in Thai population.     

Von Hippel-Lindau gene single nucleotide polymorphism (rs1642742) may be related to the occurrence and metastasis of HBV-related hepatocellular carcinoma

It is well-known that microRNAs are able to regulate the expression of target mRNAs through complementary base-pairing to their 3′-untranslated regions (3′UTR) sequences. This study aimed to investigate whether single nucleotide polymorphisms resided in the 3′UTR sequences in patients with chronic hepatitis B viruses (HBV) infection are associated with the development and metastasis of hepatocellular carcinoma (HCC). Seventeen single nucleotide polymorphisms in the 3′UTR sequence of 10 genes regulated or affected by hepatitis B virus X protein were found by bioinformatics methods. Two hundred fifteen patients with HBV-related HCC and 216 patients with chronic HBV infection were recruited. Through case-control study, only found that the von Hippel-Lindau gene rs1642742 (G>A) may be associated with the occurrence and metastasis of HCC. The ORs of the frequencies of rs1642742 A allele versus G allele were 1.424 (P = .038, 95% confidence interval [CI] = 1.019–1.989) between HBV-related HCC and chronic HBV infection group and were 2.004 (P = .037, 95%CI = 1.031–3.895) between tumor metastasis and non-metastasis group, respectively. Through multivariate regression analysis, we also found that rs1642742 AA genotype was an independent risk factor for tumor metastasis (odds ratio = 2.227, 95% CI = 1.043–4.752, P = .038) in HBV-related HCC group. Our study suggested that Von Hippel-Lindau rs1642742 contributed to susceptibility to developing HCC and correlated with tumor metastasis.     

Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort

AIM: To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China.METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms (SNPs) of KIF1B (rs17401966 and rs3748578) were chosen for the current study. All subjects were genotyped using a TaqMan real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus (HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio (OR) = 12.02; 95% confidence interval (95%CI): 6.02-24.00]. No significant association was found between the KIF1B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption (P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC (OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.     

IL-17 Genetic Variations Increase the Risk of Cirrhotic/Hepatocellular Carcinoma in Patients with Hepatitis B Virus Infection.

Background: Genetic variation in immune regulatory genes might influence the HBV infection outcome. Objective: This study aimed to determinethe association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome. Materials and Methods: 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma (C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method. Results: Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001). Conclusion: Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.     

Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between tag single nucleotide polymorphisms(tag SNPs) of interleukin-6(IL-6) gene and susceptibility to chronic hepatitis B virus(HBV) infection in a Han Chinese population.METHODS:We performed a case-control study of501 Chinese patients with chronic HBV infection and301 self-limiting HBV-infected individuals as controls.Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract highdensity tubes. Tag SNPs were identified using genotype data from the panel(Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6(rs17147230A/T,rs2066992G/T,rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed.RESULTS:Five haplotypes were involved in the analysis,with frequencies higher than 0.03. One of the haplotypes,TTAA,was significantly different between the two groups. Overall haplotype P values were:ATAA,P = 0.605,OR(95%CI) = 1.056(0.860-1.297); TGAG,P = 0.385,OR(95%CI) = 1.179(0.813-1.709); TGGG,P = 0.549,OR(95%CI) = 1.087(0.827-1.429); TTAA,P = 0.004,OR(95%CI) = 0.655(0.491-0.873); TTAG,P = 0.266,OR(95%CI) = 1.272(0.832-1.944). However,the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were:rs17147230,P = 0.696,OR(95%CI) = 1.041(0.850-1.276); rs2066992,P = 0.460,OR(95%CI)= 1.090(0.868-1.369); rs2069837,P = 0.898,OR(95%CI) = 0.983(0.759-1.274); rs2069852,P = 0.165,OR(95%CI) = 0.859(0.693-1.064). Overall genotype P values were:rs17147230,P = 0.625; rs2066992,P= 0.500; rs2069837,P = 0.853; and rs2069852,P =0.380.CONCLUSION:The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.     

Genetic biomarkers for hepatocellular cancer risk in a caucasian population

AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma(HCC)susceptibility in Caucasians. METHODS The present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two,independent,HCC-free,age/sex-matched control groups.The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation.The first control group comprised167 patients that were matched to the HCC cohort for the percentage of hepatitis B(HBV)and/or hepatitis C(HCV)infections.A second control group included192 virus-free,healthy individuals that were used to evaluate the generalizability of the identified predictive markers.All cases and controls were Caucasian.The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways.The study end-point was to assess the association between genetic variants and HCC onset. RESULTS Five genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV.According to a dominant model,reduced HCC risk was associated with three polymorphisms:ERCC1rs3212986(OR=0.46,95%CI:0.30-0.71,P=0.0005),GST-P1 rs1138272(OR=0.41,95%CI:0.21-0.81,P=0.0097),and CYP17A1 rs743572(OR=0.50,95%CI:0.31-0.79,P=0.0032).Conversely,according to a recessive model,increased HCC risk was associated with two polymorphisms:XRCC3 rs1799794(OR=3.70,95%CI:1.02-13.39,P=0.0461)and ABCB1 rs1128503(OR=2.06,95%CI:1.18-3.61,P=0.0111).These associations remained significant in a subgroup analysis,where patients were stratified according to viral status(HBV-or HCV-positive serology).Two variants exhibited a serology-specific effect:ABCB1 rs1128503(OR=4.18,95%CI:1.55-11.29,P=0.0048)showed an effect in the HBV-positive subgroup;and ERCC1 rs3212986(OR=0.33,95%CI:0.18-0.60,P=0.0003)showed an effect in the HCV-positive subgroup.Among the five markers identified,ERCC1 rs3212986(OR=0.43,P0.0001)and CYP17A1 rs743572(OR=0.73,P=0.0310)had a different distribution in patients with HCC compared to healthy individuals.With a recursive partitioning approach,we also demonstrated that significant gene-gene interactions between ERCC1rs3212986,CYP17A1 rs743572,GST-P1 rs1138272,and the previously described UGT1A7*3 predictive marker,played a role in the complex trait of HCC susceptibility.CONCLUSION We identified five polymorphisms and interactions that contributed crucially to predicting HCC risk.These findings represented an important step towards improving HCC diagnosis and management.     

Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between the tagging single nucleotide polymorphism sites(tagSNPs)of the Interleukin-18(IL-18)gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients.METHODS:Five hundred and one cases of chronic hep-atitis B virus(HBV)infection and 301 HBV natural clearance controls were studied.Two tagSNPs in the IL-18 gene(rs1946518A/C and rs574424C/G)were genotyped by the Multiplex Snapshot technique.The genotype and allele frequencies were calculated and analyzed.RESULTS:In the genotypes of rs1946518,the AA type was present at a higher frequency in the patients compared to those in the controls.Odds ratio(OR)of theAA genotype for the comparison with that of the AC and the CC genotype was 1.537(95%confidence intervals(CI):1.116-2.218,P=0.009<0.025).In pheno-types,the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls(P=0.017<0.025).OR of the allele A for the comparison with that of the allele C was 1.279(95%CI:1.045-1.567).As for the rs574424 genotypes,no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed.No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed.CONCLUSION:The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene.However,no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.     

Association between PNPLA3 gene polymorphisms and risk of hepatitis B virus-related hepatocellular carcinoma in Han population in China:a case-control study

Background and aim: Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese.

Methods: A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry.

Results: Our study indicated the clear relationship between the PNPLA3 rs2294918, rs2294919 and HBV-related HCC after control for the effects of sex, drinking and smoking. Health subjects with the PNPLA3 rs2294919?TC genotype would have a 0.605 (95% CI: 0.413, 0.886; p?=?.010) times lower odds of having HCC, and those with the rs2294918 AG genotype would have a 1.872 (95% CI: 1.256, 2.792; p?=?.002) times higher odds of having HCC, whereas the values of sex, age, drinking and smoking were fixed. In addition, CA haplotype of the haplotype block of rs738409 and rs2281135 was also associated with HBV-related HCC.

Conclusions: Our study suggested that PNPLA3 loci (rs2294918, rs2294919) were associated with HBV-related HCC in Han Chinese.     

The role of Interleukin 28B gene polymorphism in Turkish patients with hepatocellular carcinoma

Background and aim. Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC.Material and method. We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population.Results. The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P > 0.05).Conclusion. Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins.     

Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma

Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 +/- 24.1 vs 58.4 +/- 65.4 IU/L, P = 0.006) and HBV DNA levels (log(10) titre: 4.20 +/- 1.33 vs 4.80 +/- 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log(10) titre: 4.79 +/- 1.34 vs 3.27 +/- 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075-2.333] rather than in young patients (OR 0.848, 95% CI 0.645-1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC.     

DNA损伤修复基因hOGG1的遗传多态与乙肝相关性HCC的风险

目的:探讨DNA损伤修复基因hOGGI的遗传多态Ser326Cys与肝细胞癌(HCC)易感性的关系．方法:应用基因测序分型方法,分析96例HCC患者和96例健康对照hOGG1的遗传多态及与HBV感染的交互作用．结果:HCC病例组的Cys／Cys,Cys／Ser和Ser／Ser基因型分别为20．9％,44．2％和34．9％．Ser／Cys杂合子个体的OR值为1．5,Cys／Cys纯合子个体的OR值为1．9,明显高于Ser/Ser个体,表现出剂量效应．HBV感染者发生HCC的相对风险度是非HBV感染者的9倍(OR=9．2;95％CI 0．99-5．9)．对于HCC,hOGG1-Ser326Cys变异或HBV感染单一因素的OR值分别为5．5 (95％CI 0．7-240．1)和10．9(95％CI1．6-453．3),但携带变异基因者如果感染HB V,OR值则高达27．8(95％CI4．7-970．2)．结论:DNA修复基因hOGG1的Cys等位基因可能增加HCC的遗传易感性,他与HBV协同在乙肝相关性HCC的发生中起着重要作用．     

DNA修复基因XPC和XPG单核苷酸多态性与肝细胞癌易感性的关系

目的 探讨广西地区DNA修复基因XPC(Ala499Va1、Lys939G1n)和XPG(His1104Asp)单核苷酸多态性与肝细胞癌(HCC)易感性的关系.方法 采用以医院为基础的病例对照研究.经组织病理学确诊的HCC患者500例,相同地区,年龄、性别和民族频数匹配的非肿瘤患者507例.采用TaqMan MGB实时荧光定量PCR检测XPC和XPG基因多态性,比较不同基因型与HCC患病风险的关系.分别用t检验和X2检验对计量资料和计数资料进行统计分析;采用非条件的Logistic同归计算比值比(OR)及其95%可信区间(CI).结果 与XPC基因Ala499Va1位点CC基因型相比,CT或者TT基因型与HCC患病风险无相关性(校正OR=1.34,95%CI:0.85～2.12;校正OR=1.30,95%CI:0.68～2.51);与Lys939G1n位点AA基因理相比,AC或者CC基因型与HCC患病风险无相关性(校正OR=1.20,95%CI:0.78～1.85;校正OR=1.81,95%CI:0.88～3.73).与XPG基因His1104Asp位点CC基因型相比,CG或者GG基因型与HCC患病风险尢相关性(校正OR=0.85,95%CI:0.56～1.27;校正OR=1.12,95%CI:0.67～1.87).分层分析结果显示,与携带XPC基因Lys939G1n位点AA基因型女性相比,携带AC+CC基因型的女性患HCC的风险增加2.17倍(95%CI:01～4.64).结论 XPC基因Ala499Va1和Lys939G1n位点以及XPG基因His1104Asp位点SNP的单独效应可能与HCC易感性无相关性,但是XPC基因Lys939G1n位点C等位基因可协同增加女性患HCC的风险.     

Association of interferon lambda-4 rs12979860 polymorphism with hepatocellular carcinoma in patients with chronic hepatitis C infection

BACKGROUND Hepatitis C virus(HCV) infection is a public health concern worldwide.Several factors,including genetic polymorphisms,may be evolved in the progression of HCV infection to liver diseases.Interferon lambdas(IFNLs) modulate the immune response during viral infections.IFNLs induce antiviral activity,interfering in the viral replication by promoting the expression of several genes that regulate immunological functions.The interferon lambda-4(IFNL4) rs12979860 polymorphism,which is characterized by a C to T transition in intron 1,is associated with spontaneous and treatment-induced clearance of HCV infection and may play a role in the development of HCV-associated liver diseases,including hepatocellular carcinoma(HCC).AIM To investigate the association of IFNL4 rs12979860 polymorphism with fibrosis,cirrhosis,and HCC in patients with chronic HCV infection.METHODS This study was comprised of 305 chronic HCV-infected patients(53 fibrosis,154 cirrhosis,and 98 HCC cases).The control group was comprised of 260 HCVnegative healthy individuals.The IFNL4 rs12979860 polymorphism was genotyped using the TaqMan assay.Fibrosis was diagnosed based on liver biopsy findings,while cirrhosis was diagnosed through clinical,laboratory,anatomopathological,and/or imaging data.HCC was diagnosed through imaging tests,tumor,and/or anatomopathological markers.RESULTS The T allele was observed in the three groups of patients(fibrosis,cirrhosis,and HCC) at a significantly higher frequency when compared with the control group(P=0.047,P 0.001,and P=0.01,respectively).Also,genotype frequencies presented significant differences between the control group and cirrhosis patients(P 0.001) as well as HCC patients(P=0.002).The risk analysis was performed using the codominant and dominant T allele models.In the codominant model,it was observed that the CT genotype showed an increased risk of developing cirrhosis in comparison with the CC genotype [odds ratio(OR)=2.53;95%confidence interval(CI):1.55-4.15;P 0.001] as well as with HCC(OR=2.54;95%CI:1.44-4.56;P=0.001).A similar result was observed in the comparison of the TT vs CC genotype between the control group and cirrhosis group(OR=2.88;95 % CI:1.44-5.77;P=0.001) but not for HCC patients.In the dominant T allele model,the CT+TT genotypes were associated with an increased risk for progression to cirrhosis(OR=2.60;95%CI:1.63-4.19;P 0.001) and HCC(OR=2.45;95%CI:1.42-4.31;P=0.001).CONCLUSION These findings suggest that the T allele of IFNL4 rs12979860 polymorphism is associated with the development of cirrhosis and HCC in chronic HCV-infected patients.