Abstract
BackgroundTalaromycosis (TM) caused by Talaromyces marneffei (T. marneffei) is a growing public health concern. Although Toll-like receptor (TLR) genes play a critical role in the host defense against fungal infection, the influence of polymorphisms in these genes on the susceptibility of acquired immune deficiency syndrome (AIDS) patients to TM remains unknown. This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in TLR genes with TM susceptibility among patients with AIDS.MethodsAltogether 200 AIDS patients complicated with TM, 200 matched AIDS patients without TM, and 76 healthy controls (HCs) were enrolled in this case-control study. In total, 23 SNPs in the TLR2, TLR4, and TLR9 genes, which may influence the susceptibility of AIDS patients to TM, were checked by the time of flight mass spectrometry (TOF/MS) method among these Han Chinese subjects.ResultsNo significant differences in genotype or allele frequencies of selected SNPs were found among the TM group, Non-TM group, and HC group. Haplotype analysis also demonstrated no correlation of these SNPs with TM. However, subgroup analysis showed that the genotype TT and the T allele in TLR2 SNP rs1339 were more frequent in typical TM cases than controls (50.0 vs. 35.8%, 70.5 vs. 59.7%); the frequency of the GT genotype in TLR2 SNP rs7656411 was markedly higher in severe TM cases compared to controls (57.8 vs. 34.4%).ConclusionOur results demonstrate a genetic connection of TLR2 SNPs rs1339 and rs7656411 with an increased susceptibility and severity of TM among Han Chinese populations.
Highlights
Over the past 30 years, Talaromycosis (TM), a systemic mycosis caused by Talaromyces marneffei (T. marneffei), has become increasingly frequent among patients with acquired immune deficiency syndrome (AIDS), accounting for one of the most common invasive fungal diseases (IFDs) in Southeast Asia and southern China (He et al, 2020)
This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) genes with TM susceptibility among patients with AIDS
Subgroup analysis showed that the genotype TT and the T allele in TLR2 SNP rs1339 were more frequent in typical TM cases than controls (50.0 vs. 35.8%, 70.5 vs. 59.7%); the frequency of the GT genotype in TLR2 SNP rs7656411 was markedly higher in severe TM cases compared to controls (57.8 vs. 34.4%)
Summary
Over the past 30 years, Talaromycosis (TM), a systemic mycosis caused by Talaromyces marneffei (T. marneffei), has become increasingly frequent among patients with acquired immune deficiency syndrome (AIDS), accounting for one of the most common invasive fungal diseases (IFDs) in Southeast Asia and southern China (He et al, 2020). The remarkably high mortality rates owing to its challenges in prevention, diagnosis, and therapy, prompt physicians to focus on risk stratification and preemptive methods This has inspired studying on novel individual prognostic signatures, especially gene signatures, to identify AIDS patients with an increased susceptibility to TM. 11 members of the TLR superfamily (TLR1-11) have been identified in humans since the first discovery of TLR4 in late 1997 (Medzhitov et al, 1997; Zhang et al, 2004; Yarovinsky et al, 2005). Toll-like receptor (TLR) genes play a critical role in the host defense against fungal infection, the influence of polymorphisms in these genes on the susceptibility of acquired immune deficiency syndrome (AIDS) patients to TM remains unknown. This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in TLR genes with TM susceptibility among patients with AIDS
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