Онкогематология (Dec 2024)
<I>IL4</I> and <I>TLR3</I> gene polymorphism in infectious complications in patients with acute myeloid leukemia
Abstract
Background. Patients with acute myeloid leukemia (AML) are predisposed to infectious complications (IC). Single nucleotide polymorphisms in genes can affect the function and/or expression of the proteins they encode. Since the functioning of the innate immune system is under genetic control, identifying polymorphic variants that reduce the effectiveness of the immune response is a promising method for identifying patients at high risk of severe infections.Aim. To evaluate the relationship between presence of single nucleotide polymorphisms TLR3 C1234G and IL4 C589T with IC frequency in AML patients.Materials and methods. TLR3 C1234G and IL4 C589T polymorphisms were genotyped in 93 patients with AML, of which 77 (82.80 %) – de novo AML, 16 (17.20 %) – AML with previous myelodysplastic syndrome. Patients received 263 chemotherapy courses. Median age was 58 (Q1–Q3: 38–66) years, 50 (53.76 %) were men, 43 (46.24 %) were women. Sepsis and pneumonia were considered severe IC. Allele-specific polymerase chain reaction with detection of amplification products in a 3 % agarose gel was used to genotype single nucleotide polymorphisms in immune response genes.Results. Severe IC were developed in 57 (21.67 %) chemotherapy courses. It was found that in patients with the TLR3 1234GG genotype, compared with carriers of the TLR31234CC genotype, the frequency of severe IC is 4.8 times lower (odds ratio 0.21; p = 0.022). Severe IC occurred 2.3 times more often in heterozygous carriers of the IL4 C589T polymorphism than in homozygous carriers of the C allele (odds ratio 2.29; p = 0.025). In multivariate analysis, taking into account age, gender and severity of neutropenia, the TLR31234GG and IL4 589CT genotypes variants remained independent predictors of IC.Conclusion. The TLR3 1234CC and IL4589CT genotypes are associated with the risk of severe IC in AML patients.
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