Zastupljenost F508del mutacije i 5T alela politimidinskog trakta u CFTR genu kod pacijenata sa hroničnim pankreatitisom i adenokarcinomom pankreasa

Abstract

Uvod: Mutacije u CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) genu mogu biti povezane sa različitim tipovima pankreasne patologije i da nose povišen rizik za oboljenja pankreasa. Najčešća mutacija u obolelih od cistične fibroze je F508del, dok je alel 5T povezan sa atipičnim oblicima cistične fibroze. Cilj rada: Cilj ove studije bio je da se utvrdi učestalost F508del mutacije i 5T alela u genu za transmembranski regulator provodljivosti u cističnoj fibrozi (CFTR ili Cystic Fibrosis Transmembrane Conductance Regulator) u grupama pacijenata sa hroničnim pankreatitisom i adenokarcinomom pankreasa, kao i da se istraži da li ove genske varijante predstavljaju faktore rizika za nastanak bolesti pankreasa. Metod rada: Istraživanje je obuhvatilo 50 pacijenata sa hroničnim pankreatitisom i 50 pacijenata sa adenokarcinomom pankreasa, kao i 124 zdrava ispitanika. Utvrđivanje prisustva F508del mutacije i detekcija 5T, 7T i 9T alela politimidinskog trakta vršeni su na DNK izolovanoj iz periferne krvi ispitanika pomoću metode PCR-om posredovane mesto- specifične mutageneze (PSM ili PCR-mediated site-directed mutagenesis). Rezultati: Učestalost F508del mutacije u hroničnom pankreatitisu (3,0%) bila je značajno povišena (p=0,032) u odnosu na učestalost u grupi zdravih ispitanika (0,4%), dok ostale razlike u učestalostima nisu bile statistički značajne. Zaključak: Rezultati ovog istraživanja ukazuju da F508del mutacija u CFTR genu predstavlja faktor rizika za razvoj hroničnog pankreatitisa.

Introduction: Mutations in the CFTR gene may be associated with various types of pancreatic pathology and result in higher risk of pancreatic disorders. While delta F508 is the most common mutation in cystic fibrosis patients, the allel 5T is associated with atypical forms of cystic fibrosis. Study aim: The aim of this study was to establish the frequencies of F508del mutation and 5T allele in the CFTR gene in patients with chronic pancreatitis and pancreatic cancer, as well as to investigate whether these genetic variants represent risk factors for pancreatic diseases. Study methods: The study has encompassed 50 patients with chronic pancreatitis and 50 patients with pancreatic adenocarcinoma, as well as 124 healthy individuals. The analysis of F508del mutation and alleles 5T, 7T and 9T of the polythymidine tract was performed on DNA extracted from periferal blood by PCR-mediated site-direted mutagenesis (PSM) method. Results: The frequency of F508del mutation in the group of patients with chronic pancreatitis (3.0%) was significantly increased (p=0.032) in comparison to the group of healthy individuals (0.4%), while other analyzed differences were not statistically significant. Conclusion: The results of this study indicate that F508del mutation in the CFTR gene respresents a risk factor for the development of chronic pancreatitis.