Dna Methylation Profile of Selected Cytokines in Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in Caucasians with an incidence of about 1:3,000 live births. The gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein is found on the human chromosome 7 q31.2. CF is characterized by recurrent pulmonary infections, elevated sweat chloride, pancreatic and hepatic insufficiency, intestinal abnormalities, failure to thrive, diabetes, meconium ileus (MI) and other glandular defects. Chronic airway dysfunction and inflammation are the main cause of morbidity and mortality of patients. This inflammation is characterized by an increased production of pro-inflammatory cytokines in the lung. The aim of the presented study is to identify the methylation status of the promoters of inflammatory and anti-inflammatory cytokines (IL-8, TNFα IL-10) and quantitative analysis of these cytokines in cystic fibrosis patients. DNA methylation analysis of cytokine promoters was performed by the methylationspecific polymerase chain reaction. DNA fragments were amplified using specific primers for methylated or unmethylated DNA. Methylation analysis revealed statistically significant hypomethylation of IL-8 and TNFα gene promoter regions, whereas IL-10 gene promoter CpG sites were hypermethylated in cystic fibrosis patients compared to control individuals. In conclusion, identification of disease-modifying epigenetic factors at early stages of disease crucial for finding new therapeutic solutions and personalized approach in treatment of patients with Cystic Fibrosis.