Heme Oxygenase-1 Gene Promoter Polymorphism and Acute Pancreatitis
Aiste Pupine*3, Barry J. Evans2, Jean-Marc Navenot2, Zi-Xuan Wang2, Juozas Pundzius3, Giedrius Barauskas3, Zilvinas Dambrauskas3, Hwyda a. Arafat1,2
1Surgery, Thomas Jefferson University, Philadelphia, PA; 2Pathology, Thomas Jefferson University, Philadelphia, PA; 3Surgery, Lithuanian University of Health Sciences, 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. The presence of longer repeats have been shown to be associated with lower levels of HO-1 expression in vitro and is associated with many diseases in vivo. In this study, we hypothesized that the number of GT repeats in HO-1 promoter can influence the occurrence of acute pancreatitis due to its protective function. Patients with acute pancreatitis are more likely to have long repeats than controls.Methods: Acute pancreatitis (n=131) patients 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. The PCR products were analyzed by ABI 3130 genetic analyzer and the exact size of the PCR products was determined by GeneMapper software. The short allele was defined to contain 27 GT repeats or fewer. The 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) 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 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.
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