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

J Sainz1, I Salas-Alvarado, E López-Fernández

  • 1Experimental Research Unit, Virgen de las Nieves University Hospital, Granada, Spain. jsainz@ugr.es

International Journal of Immunopathology and Pharmacology
|July 22, 2010
PubMed

Insights

Genetic variations in the Tumour Necrosis Factor Receptor 1 (TNFR1) gene are linked to Invasive Pulmonary Aspergillosis (IPA) susceptibility in haematological patients. These TNFR1 polymorphisms may aid in stratifying patient risk for IPA development.

Area of Science:

  • Immunology
  • Genetics

Background:

  • Tumour necrosis factor (TNF) is crucial for immune responses against fungal infections, acting via TNF receptor 1 (TNFR1).
  • Genetic variations, specifically single nucleotide polymorphisms (SNPs), in the TNFR1 gene could influence susceptibility to infections like Invasive Pulmonary Aspergillosis (IPA).

Purpose of the Study:

  • To investigate the association between TNFR1 gene polymorphisms and susceptibility to IPA in immunocompromised haematological patients.
  • To explore the correlation between TNFR1 genetic variants, TNFR1 mRNA expression, and IPA development.

Main Methods:

  • Genotyping of three TNFR1 SNPs (rs2234649, rs4149570, rs767455) in 275 individuals (144 haematological patients, 131 controls).
  • Analysis of IPA susceptibility, TNFR1 mRNA expression levels, and galactomannan (GM) positivity in relation to specific genotypes.
  • Predictive sequence analysis of the TNFR1(-609) promoter polymorphism's effect on transcription factor binding.

Main Results:

  • TNFR1(+36(A/G)) and TNFR1(-609(G/T)) SNPs were significantly associated with IPA susceptibility (p=0.033 and p=0.018, respectively).
  • IPA patients exhibited significantly lower TNFR1 mRNA expression compared to IPA-resistant patients, with a strong correlation between the TNFR1(-609) variant and expression levels.
  • A trend towards higher galactomannan positivity was observed in patients with the TNFR1(-609G/G) genotype.

Conclusions:

  • TNFR1 genetic polymorphisms are associated with IPA susceptibility in haematological patients.
  • These findings suggest that TNFR1 variants may play a role in the innate immune response against Aspergillus and could be useful for IPA risk stratification.
  • Further validation studies with larger patient cohorts are warranted to confirm these associations.

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