A. K. Gulla1,2, A. Gulbinas3, G. Barauskas3, Z. Dambrauskas3 1Georgetown University Medical Center,Department Of Surgery,Washington, DC, USA 2Vilnius University Hospital, Santaros Clinics,Department Of Surgery,Vilnius, SANTARISKIU 2, Lithuania 3Lithuanian University Of Health Sciences, Kaunas Clinics,Department Of Surgery,Kaunas, , Lithuania
Introduction: Acute pancreatitis is a severe and frequently a life-threatening disease, which can lead to pancreatic necrosis, acute lung injury, SIRS and MODS. The inducible enzyme heme oxygenase-1 (HO-1) is an anti-oxidative, anti-inflammatory, and cytoprotective enzyme that is induced in response to cellular stress. The HO-1 promoter contains (GT)n dinucleotide repeats and is highly polymorphic in the population. In this study, we hypothesized that the number of GT repeats in HO-1 promoter can influence the occurrence of acute necrotic pancreatitis through v-cam and e-selectin expression due to its protective function. Patients with acute pancreatitis are more likely to have long repeats than controls.
Methods: Acute pancreatitis patients (n=135) and age- and sex-matched healthy controls (n=33) were studied. Peripheral blood samples from pancreatitis patients were collected on admission. Genomic DNA was extracted from the blood samples of patient and control groups. The HO-1 promoter region with the GT repeats was PCR amplified with fluorescent tagged primers and levels of cytokines were measured.
The PCR products were analyzed by ABI 3130 genetic analyzer and the exact size of the PCR products was determined by GeneMapper software. A short allele was defined as containing 27 GT repeats or fewer, whereas a long allele was more than 27 repeats.
Results: The subjects were categorized into 3 groups based on the genotype
Results: one short and one long alleles (S/L), two short alleles (S/S) and two long alleles (L/L). The presence of S/L was similar between the patient group (41.2%) and the controls (39.4%). Interestingly, 46.6% of patients were carriers of two long repeats (L/L) while 11.1% v-cam and 11.1 % e-selectins levels (p<0.05) vs 24.2% of control subjects, whereas 12.2% of patients were carriers of two short repeats vs 36.4% of control population.
Conclusion: Our data demonstrate a strong bias toward longer alleles and higher levels of v-cam and e-selectins among patients with acute pancreatitis. Thus, polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute pancreatitis. Further studies are now underway to analyze the pancreatic levels of HO-1 protein in acute pancreatitis patients and controls and to determine whether the presence of the short alleles facilitate HO-1 upregulation and consequently promote its protective anti-inflammatory function in acute pancreatitis.
