Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics
C B Lupiañez1, L M Canet1, A Carvalho2
1Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
Infection and Immunity
|December 16, 2015
Summary
Genetic variations in immune-related genes, like IFNγrs2069705, impact invasive aspergillosis risk in immunocompromised patients. These single-nucleotide polymorphisms (SNPs) can improve disease prediction models, aiding in tailored prophylaxis strategies.
Area of Science:
- Immunogenetics
- Infectious Diseases
- Oncology
Background:
- Immune-modulating single-nucleotide polymorphisms (SNPs) are implicated in cancer-related infection susceptibility.
- Invasive aspergillosis (IA) poses a significant threat to immunocompromised individuals, particularly those undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Purpose of the Study:
- To investigate the association between 36 SNPs in 14 immune-related genes and the risk of IA.
- To determine if genotyping these SNPs can enhance the prediction of IA risk in immunocompromised patients.
Main Methods:
- A case-control association study involving 781 immunocompromised patients (149 with IA).
- Genotyping of 36 SNPs within immune-related genes.
- In vitro assays to assess the functional impact of the IFNγrs2069705 SNP on macrophage function and cytokine production.
Main Results:
- IL4Rrs2107356 and IL8rs2227307 SNPs were associated with increased IA risk (ORs 1.92 and 1.73, respectively).
- IL12Brs3212227 and IFNγrs2069705 SNPs were associated with decreased IA risk (ORs 0.60 and 0.63, respectively).
- The IFNγrs2069705C allele enhanced macrophage-mediated fungal neutralization and increased IFNγ and TNF-α production.
- Incorporating associated SNPs into clinical models significantly improved IA prediction (AUC 0.659 vs. 0.564).
Conclusions:
- Specific immune-related SNPs, notably IFNγrs2069705, are significantly associated with invasive aspergillosis risk.
- Genotyping these SNPs can substantially improve disease risk prediction models.
- These findings support the development of risk-adapted prophylaxis and diagnostic strategies based on genetic profiles.
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