Influence of the Polymorphism C-509T in the Gene Promoter on the Response to Montelukast.

Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine with a key role in asthma airway inflammation and remodeling. Since elevated levels of this cytokine in airways might be associated with response to asthma therapy, the aim of this study was to investigate whether the presence of the polymorphism C-509T in the promoter of the gene is associated with response to montelukast. A group of 102 asthmatic patients was genotyped for the presence of the C-509T polymorphism by DNA sequencing and subjected to induced sputum sampling. Cells from sputum samples and BEAS 2B cells were treated with montelukast and endogenous expression was measured by quantitative real-time polymerase chain reaction. The promoter activity was analyzed by luciferase assays in BEAS 2B cells transfected with constructs carrying variants -509C and -509T of the gene promoter. After treatment with montelukast, the decrease in gene expression was greater for the -509TT genotype (58.9%) than for the -509CC and -509CT genotypes (49.6% and 31.8%, respectively) ( = 0.071). In BEAS 2B cells, expression of endogenous was reduced by about 27% after montelukast treatment, while luciferase activity of both promoter variants was increased after montelukast treatment (-509C allele: 48.3%,  = 0.060; and -509T allele: 100.5%,  = 0.062). A more intensive response was registered in the promoter containing the -509T allele, which had 135% higher activity than the -509C variant ( = 0.035). This study showed that the presence of the -509T allele in the promoter might modulate effects of montelukast on gene expression, but future studies are necessary, taking into consideration other genetic and nongenetic factors. It is of potential importance for clinical management of asthma to clarify the influence of the C-509T polymorphism on the response to treatment with montelukast.