Evaluation of death pathway genes <i><scp>FAS</scp></i> and <i><scp>FASL</scp></i> polymorphisms in chronic <scp>HBV</scp> infection

Zamani, Ayse Gul; Barlas, İbrahim Ömer; Durakbasi-Dursun, G.; Ural, Onur; Erdal, Emin; Yıldırım, Mahmut Selman

doi:10.1111/iji.12056

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…Several studies have shown that FAS -670 AA genotype and A allele were associated with liver diseases such as autoimmune hepatitis and development of cirrhosis ( 30 , 31 ), Liver graft rejection ( 32 ) and Hepatitis C ( 33 ). Zamani et al ( 34 ) showed that FAS-670 A/G polymorphism was associated with chronic HBV infection, while FASL IVS2nt-124 A/G polymorphism was not; also FAS -1377 G/A and FASL-844 C/T genotypes were likely to play a substantial role in HBV infection outcome.…”

Section: Discussionmentioning

confidence: 99%

FAS and FAS-Ligand Promoter Polymorphisms in Hepatitis B Virus Infection

et al. 2015

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Background:The FAS and FAS-Ligand (FASL) system is an important apoptosis pathway in the liver. The FAS-mediated pathway functions by binding the FASL on the activated cytotoxic T lymphocytes and Natural Killer (NK) cells to the FAS receptor on infected hepatocytes. FAS and FASL polymorphisms, which are related to apoptosis, might influence the outcome of Hepatitis B Virus (HBV) infection.Objectives:Thus, the present study aimed to determine if FAS and FASL promoter polymorphisms are associated with the clinical outcome of HBV infection.Patients and Methods:DNA samples were obtained from the infected individuals including chronic carrier (n = 50), chronic hepatitis (n = 50), cirrhosis (n = 25), naturally recovered (n = 26) and compared with those of their matched healthy controls (n = 100). Genotyping for polymorphisms of FAS-670 A/G and -1377 G/A, and FASL -844 C/T was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays.Results:Multiple analyses for genetic association of FAS and FASL polymorphisms were not statistically different between HBV patients (n = 125) and healthy controls (n = 100). However, genotype and allele frequencies of FASL-844 C/T were significantly different between recovered individuals and patients with cirrhosis (P = 0.02 and P=0.01, respectively). Whereas, FAS-670A/G and -1377G/A polymorphisms were similarly distributed in these two groups (P = 0.8 and P = 0.47, respectively).Conclusions:The current study results showed that bearing -844T allele in FASL promoter region has a protective effect on cirrhosis and is involved in recovery from infection. In conclusion, it is proposed that HBV infection outcome might be influenced by FASL-844C/T polymorphism through alteration in apoptosis of hepatocytes.

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Section: Discussionmentioning

confidence: 99%

FAS and FAS-Ligand Promoter Polymorphisms in Hepatitis B Virus Infection

et al. 2015

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“…Dysregulation of apoptosis contributes to various liver diseases such as hepatocellular carcinoma, viral and autoimmune hepatitis, ischaemia/reperfusion injury, toxic liver damage and acute liver failure [4][5][6][7]33]. After cholestatic injury, the initial insult can be directed towards hepatocytes and cholangiocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Recent data have identified that dysregulation of apoptosis is a principal contributor to the pathogenesis of various liver diseases [5][6][7]. In cardiac diseases, apoptosis is also important in modulating heart function, and interrupting apoptosis can attenuate or prevent heart failure [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte apoptosis contributes to pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated mice

et al. 2014

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Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunctions, electrophysiological changes and macroscopic structural changes. However, the underlying mechanisms of this syndrome remain unclear. A possible role of myocardial apoptosis in the pathogenesis has not been previously examined. We hypothesized that dysregulation of apoptotic signalling participates in cardiac dysfunction in the cirrhotic heart. Therefore, we evaluated apoptotic pathways in the hearts of mice with chronic BDL (bile duct ligation). A cirrhotic cardiomyopathy model was induced by BDL in mice. Left ventricular geometry and volumes were evaluated by MRI. Intrinsic and extrinsic apoptotic pathways were evaluated by immunohistochemical staining and Western blot analysis. Fas-mediated apoptosis was inhibited by in vivo administration of an anti-FasL (Fas ligand) monoclonal antibody, and subsequently cardiac contractility was measured in isolated cardiomyocytes. BDL-mice showed significantly more PARP [poly(ADP-ribose) polymerase] staining than sham controls (18.2±11.4 compared with 6.7±5.3; P<0.05). Fas protein expression and PARP cleavage were activated, whereas FLIP (Fas-associated death domain-like interleukin 1β-converting enzyme-inhibitory protein) was decreased compared with sham controls. The Bcl-2/Bax ratio was increased in BDL-mice compared with sham controls. Anti-FasL monoclonal antibody injection in BDL-mice improved systolic and diastolic dysfunctions in cardiomyocytes, but had no effect in sham controls. A net pro-apoptotic balance exists in BDL hearts, mainly mediated by activation of the extrinsic pathway, and abrogation of apoptosis improved contractility. These results suggest that apoptosis contributes to depressed cardiac contractility in a murine model of cirrhotic cardiomyopathy.

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“…However, death of HBV-infected hepatocytes is thought to occur primarily through Fas-mediated killing. Soluble Fas (sFas) and soluble Fas ligand (sFasL) have been shown to inhibit hepatocyte apoptosis [42–44] allowing for the persistence of HBV in hepatocytes [45]. The Fas pathway is also involved in the apoptosis of activated T cells as a mechanism to maintain peripheral tolerance.…”

Section: Introductionmentioning

confidence: 99%

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles

Shata

Abdel-hameed

Rouster

et al. 2019

PAI

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Background: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFβ1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. Methods: Levels of soluble Fas/FasL, TGFβ1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). Results: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFβ−1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1β. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. Conclusion: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.

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Evaluation of death pathway genes FAS and FASL polymorphisms in chronic HBV infection

Cited by 6 publications

References 25 publications

FAS and FAS-Ligand Promoter Polymorphisms in Hepatitis B Virus Infection

FAS and FAS-Ligand Promoter Polymorphisms in Hepatitis B Virus Infection

Cardiomyocyte apoptosis contributes to pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated mice

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles

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