Association of polymorphisms in the TLR4 gene with the risk of developing neutropenia in children with leukemia

Abstract

Infections are a major cause of morbidity and mortality in children with acute lymphoblastic leukemia (ALL). Susceptibility to infections increases as the neutrophil count decreases. Despite identical treatment patients vary considerably in the number of neutropenic episodes. Toll-like receptor 4 (TLR4) has been shown to have a role in inhibiting apoptosis of neutrophils. Therefore, we hypothesized that polymorphisms in the TLR4 gene may influence the number of chemotherapyinduced neutropenic episodes. Eight single-nucleotide polymorphisms (SNPs) of the TLR4 gene were determined in 194 children aged 0-17 years, who were diagnosed with ALL. We compared the genotype distributions of the SNPs with the frequency of neutropenic episodes during treatment with chemotherapeutic regimens. The number of neutropenic episodes varied from 0 to 17, with a median of four neutropenic episodes. Four SNPs in the TLR4 gene (rs10759931, rs11536889, rs1927911 and rs6478317) were associated with an increased risk of developing chemotherapy-induced neutropenia, each sustaining correction for multiple testing. Further studies are required to elucidate whether pediatric patients with ALL with the particular SNPs in the TLR4 gene also experience more infections and would benefit from prophylactic antibiotic treatment, by a reduction of morbidity and mortality due to infections.

The association between toll-like receptor 4 polymorphisms and diabetic retinopathy in Chinese patients with type 2 diabetes

“…A similar result was found in the previous study, which indicated that rs1927911 was not associated with DR in an Indian and a South Korean population 20 32. Contrary to our observation, rs1927911 was found to be associated with a lower risk of myocardial infarction in an American population, and the SNP was reported to have an increased risk of developing chemotherapy-induced neutropenia in a Caucasus population 33 34. With respect to the TLR4 variant rs10759931, no significant difference between the two groups was revealed concerning the allele and genotype of this SNP.…”

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

“…Another study showed a combined effect of TLR4 3725G>C and miR-146a G>C gene polymorphisms for risk of gastric atrophy, but not for GC [43]. Our data on TLR4 3725G>C genotype frequencies are comparable to the reported frequencies in leukemia study on Caucasian population [44]. We did not find significant association between TLR4 3725G>C genotypes and HRAG or GC.…”

Association of Toll-Like Receptor 4 Polymorphisms with Diabetic Foot Ulcers and Application of Artificial Neural Network in DFU Risk Assessment in Type 2 Diabetes Patients

“…Various epidemiological studies also suggest that these SNPs in the innate immune system may influence the risk of patients to serious infection [36]. Budulac et al (2011) have shown the association of TLR4 polymorphisms with infection status and disease outcome in Chronic Obstructive Pulmonary Disease while Miedema et al (2011) showed that TLR4 polymorphisms were associated with risk of developing neutropenia in leukemic children [37, 38]. The remaining three SNPs were rs11536858, rs1927911, and rs1927914 of TLR4 gene and have been shown to be associated with several inflammatory diseases including cancer [10].…”