Genetic variants and the risk for invasive mould disease in immunocompromised hematology patients

Single-nucleotide polymorphisms (SNPs) appear to influence the risk of invasive mould disease (IMD) in immunocompromised patients. This raises the question of whether genetic risk prediction can be used to alter clinical practice. This review focuses on the current status of genetic association studies regarding invasive fungal disease among hematology patients, with an emphasis on IMD.

Many studies have shown that SNPs in genes encoding cytokines, chemokines, and their receptors can increase the risk for IMD. Greater emphasis has recently been placed on SNPs in pattern-recognition receptors, including Toll-like receptor 4 (TLR4) and dectin-1. An association has been found between SNPs in TLR4 and dectin-1 and invasive aspergillosis, which has been strengthened by biological evidence from in-vitro and in-vivo studies that showed a loss of function in the presence of the SNP. Nevertheless, despite improving our understanding of host antifungal defenses in immunocompromised hosts, clinical applicability is still a long way off. Current genetic associations need further validation, as virtually all studies suffer methodological limitations such as small sample size, heterogeneity of cohorts, selection bias, ill defined outcome measure, and statistical flaws, mainly the lack of adjustments for multiple comparisons.

Genetic variations in immune genes are associated with the risk for IMD among hematology patients although inconsistencies are frequently reported. The next step will be to select consistent SNPs and test them for their value in assessing risk in larger, better designed multicenter studies that will necessitate collaboration of multiple institutions in national or international consortia.