Association of Interleukins Genes Polymorphisms with Multi-Drug Resistant Tuberculosis in Ukrainian Population

Abstract

Introduction: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. Material and methods: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Results: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Conclusions: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

Genetic Polymorphisms of Il-17a in Association With the Risk of Pulmonary Tuberculosis in Iraqi Patients

“…Furthermore, the rapid non-detection of MDR-TB, which is necessary to begin developing an appropriate treatment manner to control MDR-TB [22]. Perhaps, due to the long path of processing with the second-line anti-inflammatory drugs (ATDs) have higher side effects and cost, Shaji et al and Butov et al [23,24] assume that Th1-lymphocyte activity decrease in this group of patients. In the present study, decrease level of IL-17A in MDR may be due to stopping the treat before the end of the prescribed period or leaving some doses and irregularity in the treatment allows the bacteria to become resistant to antibiotics, making the disease more serious and difficult to treat, affecting the function of the immune system, and thus reduce the level of IL-17A in MDR-TB patient.…”

Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis in Han Chinese from Hubei Province

“…Many human immunogenetic factors, such as IFN‐gamma receptor (Lü et al., ; Park et al., ), NRAMP1 (Wu et al., ), VDR (Lee et al., ), TLR (Salie et al., ), LMP/TAP (Roh, Yoon, Shin, Song, & Park, ), IL‐10 (Liang, Guo, Li, & Kong, ) and HLA gene polymorphisms (Harfouch‐Hammoud & Daher, ; Kettaneh et al., ), have been confirmed as risk or resistance factors to tuberculosis in populations of various ethnic and geographical origins (Taype, ShaVipzzaman, Accinelli, Espinoza, & Shaw, ). However, the role of host genomic susceptibility for MDR/RR‐TB has seldom been investigated (Butov et al., ; Kim et al., ; Kuranov et al., ; Marwoto et al., ; Park et al., ; Rathored et al., ; Sharma et al., ; Singh, Balamurugan, Katoch, Sharma, & Mehra, ), which focused on human leucocyte antigens mostly.…”

The association of interferon‐gamma, interleukin‐4 and interleukin‐17 single‐nucleotide polymorphisms with susceptibility to tuberculosis

“…Different mutations in these genes can alter the recognition site of the transcription factor and can affect transcription activity, which eventually may lead to variations in cytokine production levels . Several studies revealed that polymorphisms in the promotor or other coding regions of cytokine genes have vital roles in susceptibility to TB . Growing evidence suggests that characterization of the patient's genetic determinants may play an essential role in identifying individuals at risk.…”

“…Interleukin‐4 is an anti‐inflammatory cytokine, decreases the production of IFN‐γ and induces activation of Th2 responses; these interactions result in adverse effects on TB patients. Several studies have shown that SNPs in IL‐4 (−590C/T) increase the expression of IL‐4 . Moreover, interleukin‐17 (IL‐17) plays an important role against intracellular bacterial pathogens, and high levels of IL‐17 expression are accompanied by the active form of TB .…”