Association Between Gasdermin A and Gasdermin B Polymorphisms and Susceptibility to Adult and Childhood Asthma Among Jordanians

Zihlif, Malek; Obeidat, Nathir M.; Zihlif, Nadwa; Mahafza, Tareq; Froukh, Tawfiq; Ghanim, Marcel; Beano, Hamza; Al-Akhras, Fatima M.; Naffa, Randa

doi:10.1089/gtmb.2015.0174

Cited by 17 publications

(13 citation statements)

References 32 publications

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“…11 GSDMA, GSDMC and GSDMD are all reported to have tumor suppressor activity, but GSDMB is considered to be an oncogene, associated with immune response diseases, such as childhood-onset asthma. 12, 13, 14, 15, 16, 17, 18 …”

Section: Whole Picture Of Gasdermin Familymentioning

confidence: 99%

‘Hints’ in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death

2017

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Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory caspases cleave a gasdermin D (GSDMD) protein to generate a 31 kDa N-terminal domain. The cleavage relieves the intramolecular inhibition on the gasdermin-N domain, which then moves to the plasma membrane to exhibit pore-forming activity. Thus, GSDMD acts as the final and direct executor of pyroptotic cell death. Owing to the selective targeting of the inner leaflet of the plasma membrane with the pore-forming that determines pyroptotic cell death, GSDMD could be a potential target to control cell death or extracellular bacterial infections. Intriguingly, other gasdermin family members also share similar N-terminal domains, but they present different cell death programs. Herein, we summarize features and functions of the novel player proteins in cell death, including GSDMD triggering pyroptosis, Gsdma3/GSDMA initiating autophagy/ apoptosis and DFNA5 inducing apoptosis/secondary necrosis. The gasdermin N terminus appears to be a novel pore-forming protein. This provides novel insight into the underlying roles and mechanisms of lytic or nonlytic forms of programmed cell death, as well as their potential applications in inflammation-associated diseases.

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Section: Whole Picture Of Gasdermin Familymentioning

confidence: 99%

‘Hints’ in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death

2017

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“…In three different studies we have reported significant association between many SNPS in ADAM33, GMBS, and FOXO3 genes for asthma and AR. Accordingly, the findings of this study may help in building a clear view for the genetic risk factors of AR among the Jordanian population [36][37][38].…”

Section: Discussionmentioning

confidence: 84%

Association of IL-4 Polymorphisms with Allergic Rhinitis in Jordanian Population

et al. 2020

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Background and objectives: Allergic rhinitis has complex patterns of inheritance, and single nucleotide polymorphisms, a common genetic variation in a population, exert a significant role in allergic rhinitis pathology. The current study aimed to investigate the association of Interleukin-4 (IL-4) polymorphisms with allergic rhinitis. Materials and Methods: Our study included 158 patients with allergic rhinitis and 140 healthy controls from Jordan that were genotyped for IL-4 single nucleotide polymorphisms (SNPs) C-589T (rs2243250) and T-2979G (rs2227284) using restriction fragment length polymorphism-polymerase chain reaction. Statistical analysis was conducted using IBM SPSS Statistics version 24 software. Results: The results showed that the allelic frequency of the minor alleles was 0.19 and 0.67 for C-589T (rs2243250) and T-2979G (rs2227284) in the allergic rhinitis patients, respectively, while it was 0.18 for C-589T (rs2243250) and 0.64 T-2979G (rs2227284) in the control group. The homozygous (TT) genotype of C-589T (rs2243250) was significantly associated with allergic rhinitis (p < 0.05), while there was no association of any of T-2979G (rs2227284) genotypes with allergic rhinitis. Conclusions: The results of this study indicate that genetic inter-population variation precipitates the differences in the percentages of many diseases among populations, including allergic rhinitis.

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“…The physiological function of GSDMs was unknown for decades, despite their association with different diseases such as alopecia, 43,44 asthma, [45][46][47][48] hearing loss 1,49 and cancer. 13,[50][51][52][53][54][55] The conserved N-terminal domain of all GSDMs but PJVK is shown to execute necrotic cell death.…”

Section: Gsdme Executes Necrotic Cell Death By Pore Formationmentioning

confidence: 99%

GSDME and its role in cancer: From behind the scenes to the front of the stage

Schutter

Croes

Ibrahim

et al. 2020

Intl Journal of Cancer

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Gasdermin E (GSDME), a gene originally involved in hereditary hearing loss, has been associated with several types of cancer in the last two decades. Recently, GSDME was identified as a pore-forming molecule, which is activated following caspase-3-mediated cleavage resulting in so-called secondary necrosis following apoptotic cell death, or in primary necrotic cell death without an apoptotic phase, so-called pyroptosis-like. This implication in cell death execution suggests its potential role as a tumor suppressor. GSDME also exhibited a cancer type-specific differential methylation pattern between tumor tissues and normal cells, implying GSDME gene methylation as both a pan-cancer and cancer type-specific detection biomarker. A bit paradoxically, GSDME protein expression is considered to be less suited as biomarker, and although its ablation does not protect the cell against eventual cell death, its protein expression might still operate in tumor immunogenicity due to its capacity to induce (secondary) necrotic cell death, which has enhanced immunogenic properties. Additionally, GSDME gene expression has been shown to be associated with favorable prognosis following chemotherapy, and it could therefore be a potential predictive biomarker. We provide an overview of the different associations between GSDME gene methylation, gene expression and tumorigenesis, and explore their potential use in the clinic. Our review only focuses on GSDME and summarizes the current knowledge and most recent advances on GSDME's role in cancer formation, its potential as a biomarker in cancer and on its promising role in immunotherapies and antitumor immune response.

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Association Between Gasdermin A and Gasdermin B Polymorphisms and Susceptibility to Adult and Childhood Asthma Among Jordanians

Abstract: The findings of this study confirm the previously reported association between the GSDMB gene and the risk of childhood asthma.

Cited by 17 publications

References 32 publications

‘Hints’ in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death

‘Hints’ in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death

Association of IL-4 Polymorphisms with Allergic Rhinitis in Jordanian Population

GSDME and its role in cancer: From behind the scenes to the front of the stage

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