Clinical Implication of SNVs in TLR Genes in Pediatric Patients From the Brazilian Amazon With Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy and the leading cause of childhood mortality. Single-nucleotide variants (SNVs) in key molecules of the immune system, such as Toll-like receptors (TLRs) and CD14 molecule, are associated with the development of several diseases. However, their role in ALL is unknown. A case-control study was performed with 152 ALL patients and 187 healthy individuals to investigate the role of SNVs in TLRs and the CD14 gene in ALL. In this study, TLR6 C > T rs5743810 [95% CI: 3.20, OR: 1.11–9.17, p = 0.003) and TRL9 C/T rs187084 (95% CI: 2.29, OR: 1.23–4.26, p = 0.000) seems to be a risk for development of ALL. In addition, the TLR4 A > G rs4986791 polymorphism was associated with protection from infectious comorbidities (IC 95%adj: 0.18, ORadj:0.02–1.50, p = 0.058) and the TRL1 T > G rs5743618 and TRL6 C > T rs5743810 polymorphisms with protection against death (95% IC: 0.17, OR: 0.04–0.79, p = 0.008; 95% IC: 0.48, OR: 0.24–0.94, p = 0.031, respectively). Our results show that SNVs in TLR genes may be involved in the pathogenesis of ALL and may influence clinical prognosis; however, further studies are necessary to elucidate the role of TLR1, TLR4, TLR5, TLR9 and CD14 polymorphisms in this disease.