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Heme Oxygenase-1 Polymorphism Is Associated With the Development of Necrotic Acute Pancreatitis Via Vascular Cell Adhesion Molecule-1 and the E-Selectin Expression Regulation Pathway

Gulla, Aiste MD, MHCM*†‡; Gulbinas, Antanas MD, PhD§; Dambrauskas, Zilvinas MD, PhD§; Strupas, Kestutis MD, PhD*†

doi: 10.1097/MPA.0000000000001328
Original Articles

Objectives Severe acute pancreatitis can lead to systemic complications. Here, we explore the mechanisms based on our previous study associated with the deregulation of heme oxygenase-1 (HO-1) and development of severe acute pancreatitis.

Methods Acute pancreatitis patients (n = 135) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed with an ABI 3130 genetic analyzer and GeneMapper software. A short allele was defined ≤27 dinucleotide (GT) repeats, whereas a long allele was defined >27 GT. Levels of 12 different cytokines in blood serum were measured by enzyme-linked immunosorbent assay. All samples in this study were consistently stored in −80°C.

Results Patients with the long long genotype expressed E-selectin and vascular cell adhesion molecule-1 at statistically significantly higher levels in serum compared with short short genotype or short long genotypes. Vascular cell adhesion molecule-1 and E-selectin serum levels significantly correlate with the total allele length of the HO-1 promoter region.

Conclusion Polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute necrotizing pancreatitis due to deregulation of the immune response.

From the *Institute of Clinical Medicine, Faculty of Medicine, Vilnius University;

Department of Surgery, Gastroenterology, and Urology, Vilnius University Hospital, “Santaros Klinikos,” Vilnius, Lithuania;

Department of Surgery, Georgetown University Hospital, Washington, DC; and

§Department of Surgery, Hospital of Lithuanian University of Health Sciences, Kaunas, Lithuania.

Received for publication October 22, 2018; accepted April 20, 2019.

Address correspondence to: Aiste Gulla, MD, MHCM, Department of Surgery, Gastroenterology, and Nephrourology, Vilnius University Hospital, “Santaros Klinikos,” Santariskiu St 2, Vilnius 08661, Lithuania (e-mail:

The authors declare no conflict of interest.

Online date: June 7, 2019

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