Uticaj polimorfizma gena za pankreasne proteine i faktore nekroze tumora na tok akutnog pankreatitisa

Abstract

Akutni pankreatitis ima incidencu u stalnom porastu, a varijabilnost težine bolesti i mortaliteta je izražena. Na nastanak, težinu i ishod ovog oboljenja u određenoj meri može uticati polimorfizam gena koji kodiraju pankreasne proteine i medijatore zapaljenja. Cilj ove studije je utvrđivanje povezanosti najznačajnijih varijacija gena koji kodiraju katjonski tripsinogen, inhibitor pankreasnog tripsina, transmembranski regulator sprovođenja kod cistične fibroze i faktore nekroze tumora α i β sa težinom kliničke slike ili smrtnog ishoda kod pacijenata sa akutnim pankreatitisom. Studijom je uključeno 98 pacijenata sa akutnim pankreatitisom, a dizajnirana je kao retrospektivna, tipa slučaj-kontrola. Dijagnoza i klasifikacija pacijenata prema težini bolesti su zasnovani na Atlanta klasifikacionom sistemu iz 1992. godine. Genotipizacija je sprovedena PCR-RFLP metodom. U ispitanom uzorku nije identifikovan nijedan pacijent sa PRSS1 polimorfizmom. Prisustvo SPINK1101A>G varijacije uočeno je kod samo jednog pacijenta, koji je imao tešku formu bolesti. Osobe ženskog pola obolele od akutnog pankreatitisa imaju veći rizik za razvoj teške forme bolesti ukoliko su nosioci bar jednog CFTR IVS8 9T alela (RR za 9T/9T+9T/non9T vs. non9T/non9T: 2.115; 95% CI: 1.241-3.605). Uticaj M470V na težinu i mortalitet bolesti, kao i veza sa CFTR IVS8 poly-T varijacijom, nije pokazan. Nijedan od pacijenata sa akutnim pankreatitisom nije bio nosilac CFTR R117H varijacije. Nosioci najmanje jednog varijantnog alela TNF-α -308A imaju skoro deset puta manji rizik za smrtni ishod akutnog pankreatitisa, a naročito u poznijim godinama.4 Takođe, primećena je povezanost teškog oblika bolesti sa prethodno prisutnim komorbiditetima. Kod žena obolelih od akutnog pankreatitisa prisustvo CFTR IVS8 9T alela povezano je sa težom formom bolesti. Pacijenti oboleli od akutnog pankreatitisa imaju veću šansu za smrtni ishod ako su nosioci TNF-α-308G/G alela. Povezanost varijacija PRSS1 i SPINK1 gena sa težinom i ishodom akutnog pankreatitisa nije pokazana.

The incidence of acute pancreatitis steadily increases, and the severity and mortality of the disease is markedly variable. To a certain extent, the development, severity and the outcome of acute pancreatitis are affected by genetic polymorphism of pancreatic proteins and inflammatory mediators. The aim of this study was to determine the correlation between the most significant variations of genes coding for cationic trypsinogen, pancreatic secretory trypsin inhibitor, cystic fibrosis transmembrane conductance regulator and tumor necrosis factors α and β and the severity or mortality in acute pancreatitis patients. The study was designed as a retrospective, case-control study and included 98 patients with acute pancreatitis. The diagnosis and classification of patients according to the severity of the disease were based on the 1992 Atlanta Classification System. The genotyping was carried out using the PCR-RFLP method. PRSS1 polymorphism was not detected in our investigated sample. SPINK1 101A>G variation was observed in only one patient, who was experiencing severe form of the disease. In females with acute pancreatitis, the risk of developing a severe form of the disease was increased if at least one CFTR IVS8 9T allele was present (RR for 9T / 9T + 9T / non9T vs. non9T / non9T: 2.115; 95% CI: 1.241-3.605). The effect of M470V on the severity and mortality of the disease, as well as its association with the CFTR IVS8 poly-T variation, has not been shown. None of the patients with acute pancreatitis was the carrier of CFTR R117H variation. Carriers of at least one variant TNF-α-308A allele have nearly ten times lower risk of fatal outcome of acute pancreatitis, especially at an advanced age. Also, there was association observed between severe form of acute pancreatis and previously present comorbidities. In females with acute pancreatitis, the presence of CFTR IVS8 9T allele is associated with severe form of the disease. Acute pancreatitis patients carrying TNF-α-308G/G allele have higher mortality risk. The association of PRSS1 and SPINK1 polymorphism with the severity and outcome of acute pancreatitis has not been confirmed.