TNFR1 mRNA expression level and TNFR1 gene polymorphisms are predictive markers for susceptibility to develop invasive pulmonary aspergillosis

Sainz, J.; Salas-Alvarado, I.; López-Fernández, E.; Olmedo, C.; Comino, A.; García, F.; Blanco, A.; Gómez-Lopera, S.; Oyonarte, S.; Bueno, P.; Jurado, M.

doi:10.1177/039463201002300205

Cited by 56Antifungal resistance and susceptibilityImmunodeficiency and Autoimmune DisordersFungal and yeast genetics research

TNFR1 mRNA expression level and TNFR1 gene polymorphisms are predictive markers for susceptibility to develop invasive pulmonary aspergillosis

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Sainz, J., Salas-Alvarado, I., López-Fernández, E., Olmedo, C., Comino, A., García, F., Blanco, A., Gómez-Lopera, S. +3 more·2010·International Journal of Immunopathology and Pharmacology

DOI 10.1177/039463201002300205

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Abstract

Tumour necrosis factor (TNF) is primarily secreted by monocytes/macrophages and activated T lymphocytes in response to fungal infections. TNF acts through TNF receptor 1 (TNFR1) triggering a pro-inflammatory response, and therefore plays a pivotal role in immune regulation and host immune responses. We hypothesized that single nucleotide polymorphisms (SNPs) in TNFR1 gene may influence the innate immune response against Aspergillus. Three SNPs were genotyped in 275 individuals (144 immunocompromised haematological patients with high-risk of developing IPA and 131 healthy controls): TNFR1 -383(A/C) (rs2234649) and TNFR1 -609(G/T) (rs4149570) in the 5′ UTR region, and TNFR1 +36(A/G) SNP (rs767455) in the first exon of the gene. Of the 144 haematological patients, 77 patients developed Invasive Pulmonary Aspergillosis (IPA) infection and the remaining 67 patients were not infected. TNFR1 +36(A/G) and TNFR1 -609(G/T) were associated with IPA susceptibility (p=0.033 and p=0.018, respectively). A role of TNFR1 genetic variants in the susceptibility of patients to develop IPA was also supported by the significantly lower TNFR1 mRNA expression level in IPA than in IPA-resistant patients and the strong correlation between the TNFR1 -609 genetic variant and the expression levels of TNFR1. There was also a tendency for a higher frequency of galactomannan (GM) positivity in patients with TNFR1 -609G/G genotype than in patients with TNFR1 -609G/T (p=0.0909) or TNFR1 -609T/T (p=0.0913) genotype. Predictive sequence analysis of the effects of TNFR1 -609 promoter polymorphism revealed that this SNP might play a critical role in modifying the affinity of ICSBP/IRF-8, a transcription factor that is involved in the TNFR1-mediated activation of NFκB signalling pathway. Taken together, these data suggest that TNFR1 polymorphisms influence the risk of IPA disease and might be useful for risk stratification strategies. These findings need to be confirmed in validation studies with larger samples of haematological patients.

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Polymorphisms within the tumor necrosis factor-alpha gene and its receptors are associated with susceptibility to aspergillosis.
“Polymorphisms within the tumor necrosis factor-α (TNF-α) gene [32] and its receptors [37,38] have also been associated with susceptibility to aspergillosis.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [37]

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Authors: Sainz, J., Salas-Alvarado, I., López-Fernández, E., Olmedo, C., Comino, A., García, F., Blanco, A., Gómez-Lopera, S., Oyonarte, S., Bueno, P., & Jurado, M.
Affiliations: Experimental Research Unit, Virgen de las Nieves University Hospital, Granada
Hospital Universitario Virgen de las Nieves (ES)
Haematology Department, Virgen de las Nieves University Hospital, Granada
Universidad de Granada (ES)
Blood Transfusion Centre and Tissue Bank of Granada and Almeria, Spain
ORCID: Oyonarte, S.
Jurado, M.
Venue: International Journal of Immunopathology and Pharmacology
Publisher: SAGE Publications
Published: 2010-04
Volume: 23
Issue: 2
Pages: 423-436
ISSN: 0394-6320 (ISSN-L)
2058-7384
DOI: 10.1177/039463201002300205
OpenAlex: W4848550
Cited by: 56
References: 43
Citations by year: 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 8 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 1
FWCI: 3.93
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: International Journal of Immunopathology and Pharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: Instituto de Salud Carlos III
Dirección General de Investigación Científica y Técnica
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: TNFR1, TNF receptor 1, invasive pulmonary aspergillosis, single nucleotide polymorphisms, genetic susceptibility, hematologic patients, immunocompromised patients, promoter polymorphism, galactomannan, NF-κB signaling, innate immune response, Aspergillus
MeSH terms: Interferon Regulatory Factor-8, Aspergillosis, Female, Galactose, Humans, Lung Diseases, Fungal, Male, Mannans, RNA, Messenger, Biomarkers, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptors, Tumor Necrosis Factor, Type I, Interferon Regulatory Factors

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TNFR1 mRNA expression level and TNFR1 gene polymorphisms are predictive markers for susceptibility to develop invasive pulmonary aspergillosis

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