Genetic background and immune response in paracoccidioidomycosis: A systematic review and meta-analysis of single nucleotide variants

Paracoccidioidomycosis (PCM) is a systemic fungal infection endemic to Latin America, especially Brazil, where it is considered a neglected occupational disease. Caused by Paracoccidioides spp., PCM presents a wide spectrum of clinical manifestations, ranging from localized to severe disseminated forms. This heterogeneity suggests that host-related factors, including genetic background, may influence disease development. Genetic susceptibility to infectious diseases is key to understanding differences in immune responses. In PCM, variants in immune-related genes such as cytokines and pattern recognition receptors may modulate susceptibility and disease progression. This study aimed to review the literature on the association between single nucleotide variants (SNVs) PCM susceptibility, severity, and clinical outcomes. A systematic review followed PRISMA guidelines, searching databases like MEDLINE (PubMed), Cochrane Library, LILACS, SciELO, Web of Science, and Google Scholar. Keywords related to "Paracoccidioidomycosis" and "SNVs" were used. The review included studies on SNVs and PCM susceptibility. The quality of the evidence was assessed with the Cochrane and Joanna Briggs Institute risk of bias tool. We also performed a meta-analysis of studies utilizing identical SNVs. This study is registered on PROSPERO, number CRD42025646417. Two SNVs, Interleukin 10 (IL10) and Vitamin D Receptor (VDR) showed a significant association in individual analyses, but none demonstrated a significant association in the meta-analysis. The main limitations discussed in the studies were insufficient sample size, population heterogeneity, and the composition of control groups. Although some SNVs, particularly in IL10 and VDR, showed significant associations with PCM susceptibility in individual studies, the evidence remains limited. The meta-analyses included only two studies per SNV, resulting in low statistical power and exploratory pooled estimates, largely reflecting small sample sizes, lack of replication, and methodological heterogeneity across studies.