Retrospective analysis of the association of the expression and single nucleotide polymorphisms (SNPs) of the TLR-4, PTX-3, Dectin-1 (CLEC/A) genes with development of invasive aspergillosis among hematopoietic stem cell transplant recipients with oncohematological disorders.

April 16, 2020 Uncategorized

Mycoses. 2020 Apr 14;:

Authors: Kalkanci A, Tug E, Fidan I, Guzel Tunccan O, Ozkurt ZN, Yegin ZA, Sahin EA, Kuralay Z

Abstract
OBJECTIVES: Several studies described single nucleotide polymorphisms (SNPs) on pattern recognition receptor (PRR) such as toll like receptors (TLRs), dendritic cell-associated C-type lectin-1 (Dectin-1/CLEC7A) genes of patients with invasive fungal infections (IFIs) caused by Candida and Aspergillus. We screened TLR4, Dectin-1 and PTX3 polymorphisms in a Turkish population with invasive aspergillosis (IA) underlying hematological malignancies.
METHODS: In this case control study, a cohort of 59 patients with hematological malignancies were included. There were 26 IA patients assigned by the EORTC-MSG criteria and 33 patients with no evidence of fungal disease. DNA and RNA were isolated from frozen bone marrow and serum samples. RNA levels and polymorphisms of TLR4 (rs4986790, rs4986791), Dectin-1 (rs16910526, rs7309123) and PTX-3 (rs2305619, rs3816527) were determined. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by unconditional logistic regression analysis.
RESULTS AND CONCLUSIONS: TLR4, PTX3 and Dectin-1 genes were downregulated in aspergillosis cohort under similar hematological conditions. TLR4 expression was 0.0626±0.032 in controls when compared to IA patients as 0.0077±0.014, and the difference was significant (p=0.026). There was a difference in also the PTX3 gene among IA (0.0043±0.004) and control (0.5265±0.0043) groups (p=0.035). The Dectin-1 (CLEC/A) expression was downregulated in IA group (0.1887±0.072 & 0.0655±0.010) but, not statistically significant (p>0.05). Conditional logistic regression analyses indicated that the GT genotype of rs16910526 polymorphism in Dectin-1 gene was associated with lower risk of IA. (Odds ratio=3.635, 95% confidence interval=0.690-3.138, p=0.04).

PMID: 32291814 [PubMed – as supplied by publisher]

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