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Association of the genes IL-4(C-590T), TNF-A(G-308A), PRSS1(R122H) and CFTR(DELF508C) with cytoltsis syndrome activity in patients with acute edematous pancreatitis

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Background: Acute pancreatitis is a multifactorial pathology with involving of genetic factors. The most researchers focus their attention on the polymorphism of some candidate genes of acute or chronic pancreatitis: PRSS1 (R122H), SPINK1 (N34S) or CFTR (delF508C); but do not pay enough attention to the influence of immune system because of the polymorphism of genes IL-1β, IL-4, IL-6, TNF-α and others.

Methods: The evaluation of cytolysis syndrome was performed by determining the AST and ALT activity. The De Ritis Ratio was also calculated, as one of the additional portal factors of pancreatic aggression. Molecular genetic studies have being performed on 101 patients and included the definition of polymorphic variants of four genes: IL-4 (C-590T), TNF-α (G-308A), PRSS1 (R122H) and CFTR (delF508).

Results: The distribution of genotypes among examined patients and healthy people was as follows: the gene PRSS1 (R122H) in all groups was represented by GG-genotype (100%); gene CFTR (delF508) – in 3 persons with NM-genotype (2.97%) and 98 with NN-genotype (97.03%), in the group of healthy people were met only NN carriers; gene TNF-α (G-308A) – by patients with GG-genotype (81.19%) and GA-genotype (18.81%); the gene IL-4 (C-590T) among patients was represented in 58 (57.43%) patients by CC-genotype, in 34 (33.66%) – by CT-genotype, in 9 (8.91%) – by mutation TT-genotype, among healthy – in 26 (65%), 11 (27.5%) and 3 (7.5%), respectively (χ2<1.0, p>0.05). In patients with acute edematous pancreatitis generally in the T-allele carriers (TC- and TT-genotype) of gene IL-4 AST activity exceeded that of the owners of CC-genotype 2.03 (p=0.005) and 2.77 times (p=0.011) respectively. ALT activity was also generally higher among the owners of T-allele gene IL-4 than in patients with genotype CC 1.77 (p=0.009) and 2.33 times (p=0.008).

Conclusions: The polymorphism of genes CFTR (delF508), PRSS1 (R122H) and TNF-α (G-308A) in residents of North Bukovina region is not associated with the activity of cytolysis syndrome in patients with acute edematous pancreatitis. The presence of the T-allele of gene IL-4 in these patients is characterized by higher AST (2.03-2.9 times) and ALT (1.92 and 2.11 times) activity. Abbreviattions: AP – acute pancreatitis, ECP – exacerbated chronic pancreatitis, AGP – alcoholic genesis of pancreatitis, BGP – biliary genesis of pancreatitis, AST – aspartate aminotransferase, ALT – alanine aminotransferase, PCR – polymerase chain reaction

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