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Retrospective analysis of the association of the expression and single nucleotide polymorphisms (SNPs) of the TLR4, PTX3 and Dectin‐1 ( CLEC/A ) genes with development of invasive aspergillosis among haematopoietic stem cell transplant recipients with oncohaematological disorders
Author(s) -
Kalkanci Ayse,
Tug Esra,
Fidan Isil,
Guzel Tunccan Ozlem,
Ozkurt Zubeyde Nur,
Yegin Zeynep Arzu,
Sahin Elif Ayça,
Kuralay Zeynep
Publication year - 2020
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1111/myc.13087
Subject(s) - aspergillosis , single nucleotide polymorphism , biology , genotype , odds ratio , medicine , immunology , cohort , gastroenterology , gene , genetics
Summary 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 haematological malignancies. Methods In this case‐control study, a cohort of 59 patients with haematological 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 PTX3 (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 haematological 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 = .026). There was a difference in also the PTX3 gene among IA (0.0043 ± 0.004) and control (0.5265 ± 0.0043) groups ( P = .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 > .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 = .04).