Promjena CpG metilacije u promotoru gena BACH2 u pacijenata oboljelih od upalnih bolesti crijeva

Crohnova bolest (CD) i ulcerozni kolitis (UC) pripadaju grupi kroničnih bolesti koje karakterizira upala dijelova probavnog sustava, a objedinjene su pod zajedničkim nazivom upalne bolesti crijeva. Etiopatogeneza uključuje disbiozu crijevne mikroflore i poremećaj u funkciji imunološkog sustava. Proteinski produkt gena BACH2 transkripcijski je faktor s važnom ulogom u razvoju, aktivaciji i sazrijevanju B limfocita te regulaciji i senescenciji T limfocita i proizvodnji citokina. Na taj način, BACH2 ima ključnu ulogu u održavanju imunološke homeostaze. Cjelogenomske asocijacijske studije povezale su BACH2 s brojnim autoimunim bolestima, uključujući upalne bolesti crijeva. Cilj ovog istraživanja je analizirati metilaciju DNA u promotoru gena BACH2 iz krvi osoba oboljelih od CD i UC te zdravih osoba. U tu svrhu upotrijebljeno je pirosekvenciranje nakon bisulfitne konverzije DNA te je određen stupanj metilacije CpG dinukleotida u tri fragmenta gena BACH2, od kojih se dva nalaze u promotoru, a jedan u prvom intronu gena. Rezultati pokazuju statistički značajnu promjenu u CpG metilaciji gena BACH2 između pacijenata s upalnim bolestima crijeva i zdravih ljudi te ukazuje na potencijal ovoga gena kao metilacijskog biomarkera u perifernoj krvi.Crohn's disease and ulcerative colitis belong to a group of chronic diseases characterized by intestinal inflammation, with a common name of inflammatory bowel diseases. Ethiopatogenesis includes dysbiosis of the gut microbiota and impaired function of the immune system. The protein product of the BACH2 gene is a transcription factor with a significant role in development, activation and maturation of B lymphocytes, as well as regulation and senescence of T-lymphocytes and antibody production. Therefore, BACH2 has the key role in maintaining immune homeostasis. Genome-wide association studies revealed a connection between BACH2 and a number of autoimmune diseases, including inflammatory bowel disease. In this experiment, we analysed DNA methylation in BACH2 gene promoter isolated from blood samples of individuals suffering from CD and UC as well as healthy controls. For this purpose, methylation status was determined for each CpG dinucleotide in three BACH2 fragments using bisulfite pyrosequencing method. Two of the fragments are located in the gene promoter, and the third is in the first intron of the gene. The results show statistically significant change in the methylation pattern of BACH2 gene in patients with inflammatory bowel diseases compared to healthy individuals, thus revealing the potential of this gene as a methylation biomaker in peripheral blood