Correlations between genetic polymorphism of IFN-λ family gene and HBV infection, virus replication and clearance / 生物工程学报

Hepatitis B virus (HBV) infection is one of the most serious public health problems. HBV infection could lead to hepatitis B, and even further develop into hepatic cirrhosis and hepatocellular carcinoma. Interferon lambda (IFN-λ) is a member of the interferon (IFN) family and an important cytokine for antiviral defense. There are four members in IFN-λ family, including IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4. The genetic polymorphisms in the IFN-λ genes are associated with HBV replication and treatment response of HBV patients. In this review, we summarized the roles of genetic polymorphisms of the IFN-λ genes played in HBV infection, disease progression and treatment, with the aim to better understand their function. This review could serve as a reference for the HBV prevention and treatment of HBV patients, as well as for future clinical usage.

Detection and molecular characterisation of a diagnosis escape variant associated with occult hepatitis B virus in Brazil

BACKGROUND Many studies have identified mutations in the hepatitis B surface antigen (HBsAg) as important factors limiting the ability of commercial serological assays to detect this viral antigen. However, an association between mutations in the HBsAg gene and the occurrence of occult HBV infection (OBI) in patients has not been established. OBJECTIVES To detect hepatitis B virus (HBV) DNA in patients with anti-HBc as a unique serological marker, a previously published, cost-effective TaqMan-based real-time polymerase chain reaction (PCR) test with minor groove binding probes was adapted for use in this study. The current study also aimed to investigate HBsAg mutations and genotypes of HBV in OBI at the Viral Hepatitis Ambulatory Clinic in Rio de Janeiro to determine any possible association. METHODS Intra-assay and inter-assay reproducibility were determined, and the mean coefficient of variation values obtained were 2.07 and 3.5, respectively. Probit analysis indicated that the 95% detection level was 25 IU/mL. The prevalence of OBI was investigated in 35 serum samples with an ‘anti-HBc alone’ profile from individuals who attended our clinic between 2011 and 2013. FINDINGS HBV DNA was detected in only one sample, resulting in an OBI rate of 2.9%. Nucleotide sequencing of the pre-S/S region was performed to genotype and analyse mutations within the HBsAg gene of this HBV DNA. The HBV in the OBI case was classified as sub-genotype A1, and a sequence analysis of the small S gene revealed 12 mutations in the major hydrophilic region compared to the consensus A1 sequence. Most of these mutations occurred in amino acid residues that have been reported as clinically relevant because they have been implicated in vaccine escape and/or inability to detect HBsAg by commercial serological assays. MAIN CONCLUSIONS Our study suggests the importance of specific HBsAg mutations, different from those in D, B, and C genotypes, in sub-genotype A1 HBV associated with OBI.

Effects of Interleukin-4 and Interleukin-12b Gene Polymorphisms on Hepatitis B Virus Vaccination

Abstract: Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Molecular Characterization of Hepatitis B Virus Circulating in Asymptomatic and Symptomatic Carriers in Côte d’Ivoire from 2010 to 2013.

Background: Africa and Asia remain the continent most affected by viral hepatitis B with more than1 million deaths per year. These deaths are due to complications such as cirrhosis and hepatocellular carcinoma. Several studies have shown that the rate of progression of hepatitis B to cirrhosis and liver cancer is related to the virus genotypes. Previous analyses of hepatitis B virus genome have revealed 10 genotypes (A-J) with distinct geographical distribution worldwide. Some studies have shown that the genotype E is predominant in West Africa. In Côte d'Ivoire, few data exist on the genotypes circulating. The presence of genotypes A, B, C and E has been proven but not their involvement in the development of liver complications. Aim of Study: To determine the hepatitis B virus genotypes circulating in asymptomatic and symptomatic carriers and to establish correlation between genotypes and clinical outcome in Côte d’Ivoire. Place and Duration of Study: Patients were recruited in different hospitals in Côte d’Ivoire and study was conducted in the National Reference Center for Viral Hepatitis of the Institute Pasteur from April 2010 to February 2013. Methodology: The study examined samples from 754 subjects using serological and molecular techniques. PCR and multiplex-nested PCR, using type-specific primers, were carried out to determine genotypes of hepatitis B virus in the study samples. Results: Hundred thirty nine were HBsAg-positive. Out of the 139, 49% were asymptomatic and 51% were symptomatic. Among the HBsAg-positive, the average age was 41years with 38.85% having HBV DNA in their blood samples. Sixty-four point eight percent of the latter were typeable with 97.1% as genotype E and 2.9% as genotype B. Conclusion: This study revealed a predominance of genotype E of HBV and revealed that genotype E was associated (P=0.03) with clinical Outcome.

Genotype characterization of occult hepatitis B virus strains among Egyptian chronic hepatitis C patients

Chronic hepatitis C virus [HCV] infection combined with occult hepatitis B virus [HBV] infection has been associated with increased risk of hepatitis, cirrhosis and hepatocellular carcinoma. This study aimed to determine the prevalence of occult HBV infection among Egyptian chronic HCV patients, the genotype and occurrence of surface gene mutations of HBV and the impact of co-infection on early response to treatment. The study enrolled 162 chronic HCV patients from Ismailia Fever Hospital, Egypt, who were HBV surface antigen-negative. All patients were given clinical assessment and biochemical, histological and virological examinations. HBV-DNA was detectable in sera from 3 patients out of the 40 patients who were positive for hepatitis B core antibody. These 3 patients were responsive to combination therapy at treatment week 12; only 1 of them had discontinued therapy by week 24. HBV genotype D was the only detectable genotype in those patients, with absence of [a] determinant mutations among those isolates

Overexpression of Fc receptor-like 1 associated with B-cell activation during hepatitis B virus infection

The role of B cells in the pathogenesis of hepatitis B virus (HBV) infection has not been explored in depth. In the present study, the activation status of B cells from peripheral blood of healthy controls (N = 20) and patients with acute hepatitis B (AHB, N = 15) or chronic hepatitis B (CHB, N = 30) was evaluated by measuring the expression levels of B-cell activation markers CD69 and CD86, using quantitative real-time PCR and flow cytometry. Moreover, the potential mechanism underlying B-cell activation during HBV infection was further investigated by analyzing the expression profile of FCRL1, an intrinsic activation molecule of B cells. An elevation in the levels of B-cell activation markers including CD69 and CD86 was observed in the AHB patients (44.31 ± 9.27, 27.64 ± 9.26%) compared to CHB patients (30.35 ± 11.27, 18.41 ± 6.56%, P < 0.05), which was still higher than healthy controls (12.23 ± 7.84, 8.22 ± 3.43%, P < 0.05). Furthermore, the expression of FCRL1 was found to be similar to B-cell activation markers, which was highest in AHB patients (70.15 ± 17.11%), lowest in healthy donors (36.32 ± 9.98%, P < 0.05) and half-way between these levels in patients with CHB (55.17 ± 12.03%, P < 0.05). The results were positively associated with aberrant B-cell activation. These data suggest that B cells can play a role in HBV infection, and therefore more effort should be devoted to exploring their functions.

Elevada circulación del genotipo F del virus de la hepatitis B en población infectada urbana no migratoria y migratoria de Venezuela / High circulation of genotype F hepatitis B non-migratory and migratory urban population infected virus Venezuela

Introducción: Se ha demostrado ampliamente que el genotipo F del virus de la hepatitis B (VHB) es dominante en nuestra población Amerindia. Recientemente, nosotros identificamos que en los pacientes infectados por VHB habitantes no migratorios de áreas urbanas venezolanas prevalece también el genotipo F. Objetivo: Determinar los genotipos del VHB en portadores crónicos urbanos migratorios y compararlos con el grupo no migratorio. Material y Métodos: Se investigaron 136 portadores crónicos del VHB, 110 no inmigrantes y 26 inmigrantes de origen asiático. Se evaluaron antígeno eHB y anti-eHB y los genotipos del VHB, este último mediante PCR. Resultados: En los 110 pacientes urbanos venezolanos persistió la elevada frecuencia del genotipo F (95%) con 3 casos coinfectados, 2 por genotipos A+F y 1 caso con genotipos E+F. Interesantemente, 2 casos demostraron genotipo D del VHB. Hepatitis crónica B (HCB) antígeno-e positivo fue diagnosticada en 83 pacientes (80,6%) mientras 20 casos (19,4%) presentaron HCB antígeno-e negativo. En los pacientes asiáticos infectados con un solo genotipo se identificó el C en 11 casos, el B en 4 pacientes, el F en 3 y, en 1 caso, genotipo D. Se demostró coinfección entre estos diferentes genotipos, incluyendo un caso coinfectado con genotipo E. El genotipo F se encontró coinfectando a 4 pacientes, 2 de ellos con genotipo C. Doce casos presentaron HCB antígeno e positivo y 14 pacientes HCB antígeno e negativo. De los pacientes infectados con genotipo C, 7 de ellos (54%), incluyendo los 2 coinfectados con genotipo F, presentaron HCB antígeno-e negativo. Conclusión: Es notoria la elevada circulación del genotipo F del VHB en nuestras áreas urbanas...

Introduction: It has been widely demonstrated that the genotype F of hepatitis B virus (HBV) is dominant in our Amerindian population. Recently, we identified that genotype F is prevalent in HBV non-migratory infected patients living in urban areas. Objective: To determine the genotypes of HBV in migratory chronic carriers compared to non-migratory population. Material and Methods: We investigated 136 chronic HBV carriers, 110 non-immigrants and 26 immigrants of Asian origin. We assessed hepatitis B e-antigen and antibody and HBV genotypes, the latter using PCR. Results: High prevalence (95%) of genotype F persisted among 110 Venezuelan urban patients, with 3 co-infected patients, 2 with genotypes A+F and 1 case with E+F. Interestingly, 2 cases showed HBV genotype D. Chronic hepatitis B (CHB) e-antigen positive was diagnosed in 83 patients (80.6%) while 20 cases (19.4%) showed CHB e-antigen negative. In Asian patients infected with one sole genotype, C was identified in 11 cases, B in 4 patients, F in 3, and in 1 case, genotype D. Co-infection was demonstrated among these different genotypes, including one case co-infected with genotype E. Genotype F was found in 4 co-infected patients, 2 with genotype C. Twelve cases had CHB e-antigen positive and 14 CHB e-antigen negative. From patients infected with genotype C, 7 of them (54%), including 2 co-infected with genotype F, demonstrated CHB e-antigen negative. Conclusion: It is remarkable the high circulation of HBV genotype F in our urban areas. However, given the distinct outcome described in CHB genotype F and the identification of other genotypes rather than F in urban areas, suggests that inclusion of HBV genotypes in Venezuela, should be considered standard in the management of CHB regardless the patient’s geographical origin.

A latest and promising approach for prediction of viral load in hepatitis B virus infected patients.

INTRODUCTION: Designing a rapid, reliable and sensitive assay for detection of hepatitis B virus (HBV) variants by real-time PCR is challenging at best. A recent approach for quantifying the viral load using a sensitive fluorescent principle was brushed in this study. MATERIALS AND METHODS : A total of 250 samples were collected from the outpatient unit, CLRD. Complete Human HBVDNA sequences (n = 944) were selected from the National Centre for Biotechnology Information (NCBI), primers and probes were designed and synthesized from the core, surface, and x region. Real-time based quantification was carried out using a standard kit and in-house generated standards and RT-PCR protocols. RESULTS AND DISCUSSION: The standard calibration curve was generated by using serial dilution 102 to 108. The calibration curve was linear in a range from 102 to 108 copies/ml, with an R2 value of 0.999. Reproducibility as measured by dual testing of triplicates of serum samples was acceptable, with coefficients of variation at 6.5%, 7.5%, and 10.5%. Our results showed that amplification performance was good in the case of the x-region-based design (98%). Out of 100 negative samples screened by enzyme linked immunosorbent assay and the standard RT-PCR kit, one sample was detected as positive with the in-house developed RT-PCR assay, the positivity of the sample was confirmed by sequencing the amplified product, NCBI accession {"type":"entrez-nucleotide","attrs":{"text":"EU684022","term_id":"189176131"}}EU684022. CONCLUSION: This assay is reproducible showing limited inter- and intra-assay variability. We demonstrate that the results of our assay correlated well with the standard kit for the HBV viral load monitor.

Actualización sobre hepatitis B / Upgrade in hepatitis B

El virus de la hepatitis B (VHB), es un virus DNA, el cual tiene varios antígenos, como el antígeno de superficie, y antígeno core. Colombia, es un país de baja endemicidad, sin embargo, en la Sierra Nevada de Santa Marta, está endemicidad es alta. El VHB tiene como una de sus complicaciones la hipertensión porta. En general, el VHB no atraviesa la placenta, por lo que la infección es rara in utero. Son pocos los pacientes que se presentan con HB y falla hepática fulminante y por lo tanto, son pocos los antivirales que han sido utilizados, con muy poca experiencia.

The hepatitis B virus (HBV) is a DNA virus, which has several antigens such as surface antigen and core antigen. Colombia is a country of low endemicity, however, in the Sierra Nevada of Santa Marta, is endemic is high. HBVis one of the complications of portal hypertension. In general, HBV does not cross the placenta, so the infection is rare in utero. Few patients who present with HB and fulminant hepatic failure and therefore, few antiviral drugs that have been u s e d , wi t h v e r y l i t t l e e x p e r i e n c e.

[Evaluation the relationship between alleles of+1188 in region of IL-12 with serum level of cytokine in patients with occult HBV infection]

Occult hepatitis B infection [OBI] is a form of hepatitis, which in despite of absence of detectable HBsAg, HBV-DNA is present in peripheral blood of patients. Evaluation the relationship between alleles of+1188 in region of IL-12 with serum level of cytokine in patients with occult HBV infection. In this study, the plasma samples of 3700 blood donors were tested for HBsAg and anti-HBc by ELISA. The HBsAg negative ve and anti-HBc positive samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples assigned as OBI cases and PCR-SSP and ELISA were performed to examine the polymorphisms in region of [+1188 and serum level of IL-12] respectively. The results showed that there is a significant difference in CC allele of+1188 region of IL-12 in two groups and no difference in the other evaluated genes. There is not any significant difference in serum level of IL-12 between OBI patients and controls. Our results also showed that there isn't any significant statistically relation between alleles of+ 1188 region of IL-12 with serum level of cytokine. According to the results of this study it could be concluded that OBI patients unable to produce enough quantity of IL-12 and it may be related to different IL-12 gene. CC allele was associated with OBI, hence, it seems that +1188 region of IL-12 gene has an important role in expression of IL-12 gene. Evaluation of relation between polymorphisms in +1188 region of IL-12 gene and its expression. In vitro and under mitogene affect can useful because no association was seen between serum level of IL-12 and alleles of this region

Genotypic resistance to entecavir in chronic hepatitis B patients / 대한간학회지

BACKGROUND/AIMS: The prevalence and clinical characteristics of entecavir (ETV) resistance is not well known. The aim of this study was to determine the frequency of genotypic resistance in nonresponders and virologic breakthrough (VBT) patients. METHODS: The medical records of 76 chronic hepatitis B patients treated for a least 6 months from October 2006 to October 2008 were reviewed retrospectively. We divided patients into two groups: nucleoside analogue (NA)-naive patients (n=38) and LAM experienced patients (n=38). NA-naive and LAM experienced patients received ETV at 0.5 and 1.0 mg/day, respectively. The virologic response and VBT were investigated in both groups. We used the multiplex restriction fragment mass polymorphism (RFMP) method to test genotypic resistance at the rtI169, rtT184, rtS202, rtM204, and rtM250 sites. RESULTS: Age, gender, serum ALT, and HBV DNA level before treatment did not differ between the groups. Neither VBT nor nonresponse was observed in the NA-naive group, whereas VBT and nonresponse were observed in three patients each in the lamivudine (LAM)-experienced group; all six patients had YMDD mutation at study enrollment, all three patients with VBT had genotypic resistance to ETV, but the three nonresponse patients did not have genotypic resistance to ETV. CONCLUSIONS: We suspect that VBT is mostly associated with genotypic resistance to ETV. However, nonresponse might be associated with the continuance or reselection of the YMDD mutant in LAM-experienced patients.

Correlation between hepatitis B genotypes, 1896 precore mutation, virus loads and liver dysfunction in an Indian population.

BACKGROUND/OBJECTIVES: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. METHODS: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. RESULTS: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). CONCLUSIONS: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.

Influência dos genótipos no tratamento da hepatite B: [revisão] / Influence on its genotypes of the treatment for type B hepatitis: [review]

A hepatite B pode ser classificada em oito diferentes genótipos (A-H). Esses genótipos diferem na sua distribuição geográfica mundial. No Brasil, os genótipos mais freqüentemente encontrados são o A, D e F. Algumas alterações na estrutura genética desses genótipos podem resultar em diferentes níveis de patogenicidade, sendo relacionadas com maior ou menor risco de desenvolvimento de hepatocarcinoma ou cirrose no fígado. Além das diferenças citadas, a heterogeneidade dos genótipos da hepatite B parece estar relacionada com diferenças na evolução clínica da infecção e na resposta ao tratamento antiviral. Alguns genótipos demonstraram responder melhor ao tratamento com interferon ou nucleotídeos análogos do que outros. O objetivo desta revisão foi demonstrar a importância do tratamento da hepatite B baseado nos seus diferentes genótipos. Foram revisados artigos da literatura, selecionando aqueles que abordavam questões relacionadas aos genótipos da hepatite B e sua relação com o tratamento desta infecção. Nos artigos revisados, o tratamento da hepatite B baseada em genótipos apresentou diferenças significativas. Os genótipos A e B parecem ter uma melhor resposta ao tratamento antiviral com interferon alfa e/ou lamivudina; porém, mais estudos são necessários para a consistência dessa afirmação. No entanto, através dos presentes dados, já é possível demonstrar forte associação entre genótipos e resposta antiviral. Deste modo, adaptar o tratamento aos genótipos pode promover uma melhor resposta do interferon e dos nucleotídeos na terapêutica da infecção pelo vírus da hepatite B.

Type B hepatitis can be classified according to eight different genotypes (A-H). These genotypes are different in terms of worldwide geographical distribution. In Brazil the most frequent genotypes are A, D and F. Some changes in the genetic structure of these genotypes can cause different levels of pathogenesis, being related to lower or higher risk of developing hepatocellular carcinoma or liver cirrhosis. In addition to the above mentioned differences, heterogeneity of hepatitis B genotypes seems to be related to the differences in clinical evolution of the infection and response to antiviral treatment. Some genotypes proved to have a better response to the treatment using interferon or similar nucleotides than others. This review aimed at showing the importance of treatment of type B hepatitis based on its different genotypes. Different articles from the specific medical literature were reviewed and those including genotypes for type B hepatitis and their association with the treatment of this infection were selected. In the reviewed articles genotypebased treatment of hepatitis B showed significant differences. Genotypes A and B seem to have a better response to the antiviral treatment with alpha interferon and/or lamivudine; however, more studies are necessary to confirm this assertion. Nevertheless, using the present data it is already possible to prove a strong connection between genotypes and antiviral response. Therefore, adjusting treatment to genotypes can cause a better therapeutic response from interferon and nucleotides in type B hepatitis therapy.

Phylogenetic analysis of hepatitis B virus in Pakistan

To identify the distribution pattern of Hepatitis B Virus [HBV] genotype in a group of patients and to study its phylogenetic divergence. The clinics of Gastroenterology Unit, Ziauddin University, from January to December 2006. Two hundred and one HBV infected patients were genotyped for this study. All HbsAg positive individuals, either healthy carriers or suffering from conditions such as acute or chronic hepatitis, cirrhosis and hepatocellular carcinoma were included. Hepatitis B patients co-infected with other hepatic viruses were excluded. Hepatitis B virus DNA was extracted from serum, and subjected to a nested PCR, using the primers type-specific for genotype detection. Phylogenetic analysis was performed in the pre-S1 through S genes of HBV. The divergence was studied through 15 sequences of 967bp submitted to the DBJ/EMBL/GenBank databases accessible under accession number EF584640 through EF584654. Out of 201 patients tested, 156 were males and 45 were females. Genotype D was the predominant type found in 128 [64%] patients followed by A in 47 [23%] and mixed A/D in 26 [13%]. Phylogenetic analysis confirmed the dominance of genotype D and subtype ayw2. There was dominance of genotype D subtype ayw2. It had a close resemblance with HBV strains that circulate in Iran, India and Japan

Cloning, protein expression and immunogenicity of HBs-murine IL-18 fusion DNA vaccine.

Hepatitis B is a global serious disease caused by hepatitis B virus (HBV). There is no known cure for hepatitis B. The best way to deal with the disease is by preventing with hepatitis B vaccine. However, the current protein-based vaccines made up of recombinant hepatitis B surface antigen (HBsAg) are ineffective in chronic HBV carriers and a significant number of the vaccinees do not mount the protective immune response. Novel DNA-based immunization may overcome the deficits of the protein-based immunization and may provide more effective prophylactic and therapeutic outcomes. In this study, we constructed a recombinant plasmid carrying gene encoding the HBV surface antigen (HBs) linked to DNA segment encoding full-length murine interleukin-18, i.e. pcDNA-HBs-IL-18. Immunogenicity of the DNA construct was carried out in BALB/c mice in comparison with mock, i.e. pcDNA3.1+ and vaccines comprised of pRc/CMV-HBs and pRc/CMV-HBs plus pcDNA-IL-18. All vaccinated mice revealed significant serum anti-HBs IgG response after two intramuscular injections of the vaccines at 28 day interval as compared to the level of mock. Co-administration of pRc/CMV-HBs and pcDNA-IL-18 elicited arbitrarily higher levels of anti-HBs IgG than the levels in mice immunized with pRc/CMV-HBs alone and mice that received pcDNA-HBs-IL-18 although not statistically different. Further experiments are needed to investigate the subisotypes of the IgG antibody, the kinetics of cytokine and the cell-mediated immune response. For this communication, the prototype HBs-IL-18 DNA vaccine was successfully constructed and the gene encoding murine IL-18 was successfully cloned. The latter can be co-injected with the antigen coding DNA or used as a fusion partner to the DNA for priming the immune response. The recombinant HBs and full-length IL-18 proteins have potential for other research purposes. They may be used also as standard proteins in the protein quantification assay.

Association between CCR5 Promoter Polymorphisms and Hepatitis B Virus Infection / 대한간학회지

BACKGROUND/AIMS: Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. CCR5 promoter polymorphisms are known to be associated with HIV infection. However, there has been no report on the association between CCR5 promoter polymorphism and HBV infection. Therefore, we investigated the relationship between the CCR5 promoter polymorphism and HBV infection. METHODS: A total of 377 patients were classified into two groups according to their HBV infection status: (1)he spontaneous clearance group (SC); HBsAg (-), anti-HBc (+), anti-HBs (+) (2)he chronic HBsAg (+) carrier group (CC); HBsAg (+), anti-HBc (+), anti-HBs (-). CCR5 polymorphisms were detected by employing matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)- based SNP scoring assay, termed Restriction Fragment Mass Polymorphism (RFMP), which exploits the differences in molecular masses between the common allele and rare allele bases of interest. RESULTS: We found that the genotype frequencies of CCR5 A59029G significantly differed between the SC group (n=138) and CC group (n=239) (P<0.05). The CCR5 59029A allelic genotype was associated with an increased risks of chronic infection rather than spontaneous clearance (P=0.002), and the presence of the CCR5 59029G allele was significantly associated with the spontaneous clearance of HBV (P=0.001). Strong linkage disequilibrium between the CCR5-59029 and the CCR5-59353 polymorphic variants was identified. None of the 377 subjects had the CCR5-32 bp deletion mutation. CONCLUSIONS: The CCR5 promoter polymorphisms at position 59029 might play a role in the clearance of HBV infection. This primary experimental evidence needs further studies to clarify the clinical usefulness of CCR5 promoter polymorphisms as a target for the screening or treatment of HBV infection.

Lack of Association between Hepatitis B Virus Infection and Polymorphism of Mannose-Binding Lectin Gene in Korean Population

Mannose-binding lectin (MBL) plays an important role in immune defense. This study was undertaken to investigate the association between hepatitis B virus infection and polymorphisms of MBL gene. We assessed the single nucleotide polymorphism at codon 54 in exon 1 of MBL in patients with hepatitis B virus infection and HBsAg negative controls in Korean population. A total of 498 enrolled subjects was classified into four groups. Group 1; Clearance, Group 2; Inactive healthy carrier, Group 3; Chronic hepatitis, Group 4; Liver cirrhosis. MBL gene polymorphisms at codon 54 led to three genotypes (G/G, G/A, A/A). When we divided subjects into clearance group (group 1) and persistence group (group 2-4), G/G genotype and A-allele carrier were observed in 55.6% and 44.4% in clearance group, 64.8% and 35.2% in persistence group (p=0.081), respectively. When hepatitis B virus persistent cases were divided into inactive healthy carrier (group 2) and disease progression group (group 3 and 4), MBL gene polymorphisms at codon 54 were not related to disease progression (p=0.166). MBL gene polymorphism at codon 54 was not associated with the clearance of hepatitis B virus infection nor progression of disease in chronic hepatitis B virus infection.