Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

Abstract

Toll-like receptors (TLRs) have an important role in innate immunity, and single nucleotide polymorphisms (SNPs) of TLR genes influence the risk of developing hematological malignancies. We aimed to evaluate the effect of TLR2 (rs5743708), TLR4 (rs11536889, rs4986790, rs4986791), TLR9 (rs187084, rs352140, rs5743836) on AML risk, the relation between investigated SNPs and somatic mutations, clinical features, and the overall survival of adult AML patients. All mentioned SNPs were genotyped in 511 AML cases and 503 healthy controls. DNMT3A (R882), FLT3 (D835, ITD), and NPM1 mutations’ status were investigated in AML patients. TLR4 rs4986791 was associated with an increased risk of AML under the dominant model (OR = 1.61, 95% CI: 1.001–2.59). Variant genotypes of the TLR4 rs4986790 or rs4986791 were associated with the odds of developing AML in the codominant model (OR = 3.14; 95% CI: 1.12–8.84; p = 0.032). The TLR9 rs5743836 variant genotype was associated with the NPM1 mutation (p = 0.002). The investigated SNPs were not associated with the DNMT3A, FLT3 mutations and had no significant contribution to the hazard of death after adjusting for covariates. Our findings suggest that TLR4 rs4986791 is associated with AML susceptibility. The combined variant genotypes of TLR4 rs4986790 and rs4986791 increase AML risk, the TLR9 C-G-A haplotype may represent a promising approach to predict a person’s risk for developing AML.

Keywords

• acute myeloid leukemia
• Toll-like receptor gene (<i>TLR</i>)
• susceptibility
• single nucleotide polymorphisms