Uticaj polimorfizma gena za pankreasne proteine i faktore nekroze tumora na tok akutnog pankreatitisa
The influence of genetic polymorphism for pancreatic proteins and tumor necrosis factors on course of acute pancreatitis
Author
Radosavljević, IvanMentor
Đorđević, NatašaCommittee members
Janković, SlobodanJevđić, Jasna
Karamarković, Aleksandar
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Show full item recordAbstract
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 u...očeno 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.
Faculty:
Универзитет у Крагујевцу, Факултет медицинских наукаDate:
08-02-2019Projects:
- Pharmacological analysis of effects of biologically active substances on isolated smooth muscles from human gastrointestinal and urogenital tract (RS-MESTD-Basic Research (BR or ON)-175007)
- Molecular, biochemical and immunological tumor diagnosis (RS-MESTD-Basic Research (BR or ON)-175056)