Evaluatin of Association of rs4986790 and rs4986791 Single-Nucleotide Polymorphisms in TLR4 with Febrile Neutropenia in Childhood Acute Lymphoblastic Leukemia

Abstract

Background: Infections cause significant complications and, in severe cases, death in patients with childhood Acute Lymphoid Leukemia (ALL). Toll-like receptors (TLRs) play a crucial role in initiating innate immune responses. Previous studies indicate the role of TLR4 gene polymorphisms in the increased risk of infection in adults and children. This study investigated the potential association between Asp299Gly (rs4986790) and Thr399Ile (rs4986791) polymorphisms in the TLR4 gene with febrile neutropenia, as a hallmark of infection, in children with ALL. Material and Methods: This cross-sectional study was performed on 51 ALL child patients, with age (mean±s.d.) 5.2 ± 3.4 years.  Genotype analysis of rs4986790 and rs4986791 polymorphisms in the TLR4 gene was evaluated by ARMS- PCR and PCR-RFLP, respectively. Statistical analysis was performed using SPSS software. P-values <0.05 were considered significant. Results: The rs4986790 and rs4986791 polymorphisms were detected in 5.8% and 7.8% of ALL patients, respectively. The mean of recurrence of febrile neutropenia in patients without TLR4 rs4986790 and TLR4 rs4986791 polymorphisms was 3.1 ±2 and 3 ±1.9, respectively, while in patients with TLR4 rs4986790 and TLR4 rs4986791 polymorphisms, they were 4.6 ± 3 and 5.2 ±2.8, respectively (P = 0.09). No association was found between TLR4 rs4986790 and rs4986791 polymorphisms and the number of febrile neutropenia recurrences (P = 0.4). Conclusion: Although rs4986790 and rs4986791 polymorphisms were detected in ALL patients, these polymorphisms were not associated with febrile neutropenia. It is suggested to investigate other polymorphisms in immune system-related genes and their role in febrile neutropenia.