Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

Doğanay, Levent; Fejzullahu, Arta; Katrinli, Şeyma; Enç, Feruze Yılmaz; Öztürk, Oğuzhan; Çolak, Yaşar; Ulasoglu, Celal; Tuncer, İlyas; Doğanay, Gizem Dinler

doi:10.3748/wjg.v20.i25.8179

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…Numerous studies previously associated DRB1*07:01 with both vaccine non-response and persistent HBV infection in multiple ethnic populations[ 77 - 79 ]. Furthermore, DRB1*07 was also associated with decreased risk of HBV-related cirrhosis in a Turkish population[ 80 ], implicating a DRB1*07 -associated hypo-immune profile against HBV.…”

Section: Gwas For Immune Response To Hepatitis B Vaccinementioning

confidence: 99%

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Akçay

Katrinli

Özdil

et al. 2018

WJG

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The clinical outcome of hepatitis B virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure, depending on the success or failure of immune response to HBV. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

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Section: Gwas For Immune Response To Hepatitis B Vaccinementioning

confidence: 99%

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Akçay

Katrinli

Özdil

et al. 2018

WJG

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“…To address the above challenge on the poor performance of distinguishing stages by molecular signatures at the individual expression level, we introduced biomarkers with network information. Generally, a complex disease results from dysfunctions, not in individual molecules but via a systematic interplay of multiple molecules and even biological functions (Barabási and Oltvai, 2004; Elkington, 2006). To obtain non-invasive biomarkers to precisely and specifically distinguish HCC stages from other disease stages during the progression of HBV-associated carcinogenesis, we developed an algorithm to identify stage-characterized biomarkers based on network information (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Dynamic edge-based biomarker non-invasively predicts hepatocellular carcinoma with hepatitis B virus infection for individual patients based on blood testing

Fang

et al. 2019

Journal of Molecular Cell Biology

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Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths in Asia and Africa. Developing effective and non-invasive biomarkers of HCC for individual patients remains an urgent task for early diagnosis and convenient monitoring. Analyzing the transcriptomic profiles of peripheral blood mononuclear cells from both healthy donors and patients with chronic HBV infection in different states (i.e. HBV carrier, chronic hepatitis B, cirrhosis, and HCC), we identified a set of 19 candidate genes according to our algorithm of dynamic network biomarkers. These genes can both characterize different stages during HCC progression and identify cirrhosis as the critical transition stage before carcinogenesis. The interaction effects (i.e. co-expressions) of candidate genes were used to build an accurate prediction model: the so-called edge-based biomarker. Considering the convenience and robustness of biomarkers in clinical applications, we performed functional analysis, validated candidate genes in other independent samples of our collected cohort, and finally selected COL5A1, HLA-DQB1, MMP2, and CDK4 to build edge panel as prediction models. We demonstrated that the edge panel had great performance in both diagnosis and prognosis in terms of precision and specificity for HCC, especially for patients with alpha-fetoprotein-negative HCC. Our study not only provides a novel edge-based biomarker for non-invasive and effective diagnosis of HBV-associated HCC to each individual patient but also introduces a new way to integrate the interaction terms of individual molecules for clinical diagnosis and prognosis from the network and dynamics perspectives.

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“…As host-virus immune interaction might be influenced by viral genotype. Doganay et al reported [27] that DQB1 05:01 was associated with chronic active disease where all patients were exclusively genotype D. As we know, genotype B and C were dominantly prevalent in Chinese HBV infections while the HBV genotype in European and American infections were mainly A and D. Therefore, the difference in the HBV virus genotype in different regions may also one important factor for HBV susceptibility and could account for the heterogeneity of the DQB1 gene polymorphism and HBV infection outcomes.…”

Section: Discussionmentioning

confidence: 99%

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection

Ou¹,

Xu²,

Yu³

et al. 2018

J Transl Med

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BackgroundInfection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections.MethodsThis study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case–control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance.ResultsWe found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02.ConclusionDBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1716-z) contains supplementary material, which is available to authorized users.

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Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

Abstract: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Cited by 17 publications

References 37 publications

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Dynamic edge-based biomarker non-invasively predicts hepatocellular carcinoma with hepatitis B virus infection for individual patients based on blood testing

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection

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