Association between Toll-like receptor 4 polymorphism and Acute Lymphoblastic Leukemia susceptibility in Saudi Arabian patients

Abstract

Objective: Toll-like receptors (TLRs) play a critical role in initiating an immune response against infections. The present study aimed to investigate the relationship between Single Nucleotide Polymorphisms (SNP) and the expression of TLR4 gene with the risk and prognosis of acute lymphoblastic leukemia (ALL) in the Saudi population. Methods: SNPs at rs4986790 (A/G) rs1927906 (C/T) and rs7856729 (G/T) were genotyped in 265 subjects, including150 patients and 115 community-matched healthy controls from a Saudi ethnic population. Using quantitative reverse transciptase PCR, the mRNA expression of TLR4 was compared between the two subgroup. Results: Single nucleotide polymorphisms of the TLR4 in the 3’ UTR region and the fourth exon, were found to be associated with the risk of ALL. Individuals carrying the heterozygous genotype for the rs4986790 AG are significantly decreased ALL risk (OR: 0.313; 95% CI: 0.150–0.655; P = 0.002). Furthermore, the CT genotype of the rs1927906 was significantly associated with the protection against ALL (OR: 0.305; 95% CI: 0.167–0.557; P = 0.00007). Moreover, the mRNA expression of TLR4 was significantly higher in patients with ALL than in healthy individuals (P < 0.001). Conclusion: This is the first study focusing on the TLR4 gene variants in leukemia patients in the Saudi population.These results suggested that TLR4 rs4986790 (AG) and rs1927906 (CT) polymorphisms may play an important protective role against ALL. In addition, the increased expression of the TLR4 gene in leukemic samples could serve as a novel potential prognostic factor for this receptor, especially in ALL cases.

Keywords

• Acute lymphoblastic leukemia
• Polymorphism
• Gene expression
• Toll like receptor
• Saudi population