Interleukin-16 Gene Polymorphisms Are Considerable Host Genetic Factors for Patients’ Susceptibility to Chronic Hepatitis B Infection

Host genetic background is known as an important factor in patients’ susceptibility to infectious diseases such as viral hepatitis. The aim of this study was to determine the effect of genetic polymorphisms of interleukin-16 (IL-16) cytokine on susceptibility of hepatitis B virus (HBV) infected patients to develop chronic HBV infection. Genotyping was conducted using PCR followed by enzymatic digestion and RFLP (restriction fragment length polymorphism) analysis. We genotyped three single nucleotide polymorphisms (SNPs) in the Il-16 gene (rs11556218 T>G, rs4778889 T>C, and rs4072111 C>T) to test for relationship between variation at these loci and patients’ susceptibility to chronic HBV infection. Allele frequency of Il-16 gene rs4072111 and rs11556218 was significantly different between chronic HBV patients and healthy blood donors. Genotype frequency of rs4778889 polymorphism of Il-16 gene was significantly different when chronic HBV patients and HBV clearance subjects were compared. Our results showed that Il-16 gene polymorphisms are considerable host genetic factors when we chase biomarkers for prognosis of HBV infected patients.

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Single Nucleotide Polymorphisms rs2227284, rs2243283 and rs2243288 in the IL-4 Gene Show no Association with Susceptibility to Chronic Hepatitis B in a Chinese Han Population

Infection International ◽

10.1515/ii-2017-0068 ◽

2014 ◽

Vol 3 (1) ◽

pp. 16-21

Author(s):

Qin Zhou ◽

Yu-feng Gao ◽

Xiao-miao Zhao ◽

Fa-ming Pan ◽

Xu Li

Keyword(s):

Hepatitis B ◽

Hbv Infection ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

P Values ◽

Chronic Hbv Infection ◽

Han Population ◽

B Virus ◽

Chronic Hbv

Abstract Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of the interleukin-4 (IL-4) gene and outcome of hepatitis B virus (HBV) infection in a Chinese Han population. Methods Total of 501 patients with chronic hepatitis B virus (HBV) infection and 301 controls with selflimiting HBV infection were studied. Three tag SNPs in the IL-4 gene (rs2227284G/T, rs2243283C/G and rs2243288A/G) were genotyped by the Multiplex snapshot technique. The genotype and allele frequencies were calculated and analyzed. Results The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were: rs2227284, P = 0.655, odds ratio (OR) [95% confidence interval (CI)] = 1.070 (0.793-1.445); rs2243283, P = 0.849, OR (95% CI) = 0.976 (0.758-1.257); rs2243288, P = 0.659, OR (95% CI) = 1.060 (0.818-1.375). Overall genotype P values were: rs2227284, P = 0.771; rs2243283, P = 0.571; rs2243288, P = 0.902. There were no statistically significant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs also had no significant differences between the two groups. Conclusions The three tag SNPs of IL-4 were not associated with the outcome of HBV infection in the Han Chinese population.

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Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression

BMC Medical Genomics ◽

10.1186/s12920-021-00907-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Zheng Zeng ◽

◽

Hankui Liu ◽

Huifang Xu ◽

Haiying Lu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Genetic Factors ◽

East Asian ◽

Hbv Infection ◽

Healthy Controls ◽

Host Genetic ◽

Host Genetic Factors

Abstract Background Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Methods Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection. Results There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10−6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10−6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10−6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10−6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population. Conclusions In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

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Clinical Relevance of HLA Gene Variants in HBV Infection

Journal of Immunology Research ◽

10.1155/2016/9069375 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 20

Author(s):

Li Wang ◽

Zhi-Qiang Zou ◽

Kai Wang

Keyword(s):

Hepatitis B ◽

Disease Progression ◽

Association Studies ◽

Hbv Infection ◽

Genome Wide Association Studies ◽

Gene Variants ◽

Nucleotide Polymorphisms ◽

Hla Polymorphism ◽

Chronic Hbv Infection ◽

Chronic Hbv

Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.

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Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

Journal of Clinical Medicine ◽

10.3390/jcm10132926 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2926

Author(s):

Sirinart Sirilert ◽

Theera Tongsong

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Pregnancy Outcomes ◽

Natural Course ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv ◽

Adverse Pregnancy ◽

The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

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G‐to‐A Hypermutation in Hepatitis B Virus (HBV) and Clinical Course of Patients with Chronic HBV Infection

The Journal of Infectious Diseases ◽

10.1086/598951 ◽

2009 ◽

Vol 199 (11) ◽

pp. 1599-1607 ◽

Cited By ~ 16

Author(s):

Chiemi Noguchi ◽

Michio Imamura ◽

Masataka Tsuge ◽

Nobuhiko Hiraga ◽

Nami Mori ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Clinical Course ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

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Recombinant hepatitis B core antigen carrying preS1 epitopes induce immune response against chronic HBV infection

Vaccine ◽

10.1016/j.vaccine.2003.07.014 ◽

2004 ◽

Vol 22 (3-4) ◽

pp. 439-446 ◽

Cited By ~ 31

Author(s):

Xinchun Chen ◽

Meizhong Li ◽

Xiaohua Le ◽

Weimin Ma ◽

Boping Zhou

Keyword(s):

Immune Response ◽

Hepatitis B ◽

Hbv Infection ◽

Core Antigen ◽

Recombinant Hepatitis ◽

Chronic Hbv Infection ◽

Chronic Hbv ◽

Hepatitis B Core Antigen

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Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

10.21203/rs.3.rs-52170/v3 ◽

2020 ◽

Author(s):

Xiaoyi Li ◽

Qifan Zhang ◽

Wanyue Zhang ◽

Guofu Ye ◽

Yanchen Ma ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

B Cells ◽

Hepatitis B ◽

Immune Responses ◽

Cd4 T Cells ◽

Hbv Infection ◽

Follicular Dendritic Cells ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

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