Association between interleukin-2, interleukin-4 gene polymorphisms and pulmonary multi-drugresistant tuberculosis

Abstract

Background and objective: To study the association between IL-2,IL-4 gene polymorphisms and pulmonary MDRTB. Methods. The study comprised 170 individuals: 74 patients MDRTB (1stgroup), 66 patients without – MDRTB (2ndgroup) and 30 healthy donors (3ndgroup). Serum levels of cytokines IL-2 and IL-4 were evaluated by ELISA (pg/L). Investigations of gene polymorphisms of these cytokines were performed using restriction analysis of the amplification products of specific regions of the genome. Two polymorphic variants were examined: T-330G promoter region of IL-2 and C-589T–IL-4 genes. Results. In the 1st group the levels of IL-4 and IL-2 were 7.96±0.29 and 39.34±1.14, 2nd – 11.29±0.35 and 36.20±0.89 while in 3rdgroup these values were 29.99 ±1.27 and 21.60±0.80 respectively (p<0.05). In patients with MDR TB the heterozygous genotype (79.73±4.67%(N=59) for IL-2 and 71.62±5.24%(N=53) for IL-4 genes) was higher than: 10.81±3.61%(N=8) and 14.86±4.14%(N=11) of patients had mutation genotype and normal homozygote genotype had 9.46±3.40%(N=7) and 13.51±3.97%(N=10) for IL-2 and IL-4 genes, respectively. In patients 2ndgroup the mutation homozygote genotype (65.15±5.87%(N=43) for IL-2 gene and 69.70±5.66%(N=46) for IL-4 gene) was higher than: 19.70±4.90%(N=13) and 13.64±4.22%(N=9) of patients had homozygous and normal homozygote genotype had 15.15±4.41%(N=10) and 16.67±4.59%(N=11) for IL-2 and IL-4 genes, respectively. In contrast, most of healthy donors had normal homozygous genotype with 60.00±8.94%(N=18) and low frequency of mutation genotype at 16.67±6.80%(N=5) and 23.34±7.72%(N=7) and heterozygous genotype at 23.33±7.72%(N=7) and 16.67±6.80%(N=5) for IL-2 and IL-4 genes, respectively (p<0.05). Conclusion. Compared to healthy controls patients with TB had significantly lower levels of serum IL-4 and high - IL-2. This coincided with greater frequency of heterozygous genotype in 1stgroup and mutation homozygote genotype in 2ndgroup polymorphisms C-589T and T-330G genes of IL-4 and IL-2. Further studies are warranted whether higher rate of MDRTB has a causal immunogenetic relationship to polymorphism of genes encoding for IL-2 and IL-4 than patients without MDRTB. In addition, these studies revealed a significant influence of the polymorphisms genes IL-2 and IL-4 on the changes in the population of Th-lymphocytes, clinical symptoms, relapse of TB, formation destructions in the lung, which may treatment outcomes in patients with MDRTB.