Balkan Journal of Medical Genetics

Acute pancreatitis (AP) is an acute inflammatory process of variable of etiology [1]. While etiology and pathogenesis of AP have been intensively investigated, it is still unclear why some patients progress to organ failure and others do not [2,3]. Blockage of the duodenal papilla or ampulla of Vater is the common characteristic of the disease. In developed countries, obstruction of the common bile duct by stones (38%) and alcohol abuse (36%) are the most frequent causes [4,5], but iatrogenic factors, sphincter of Oddi dysfunction and eating disorders are also important [6]. Acute pancreatitis is viewed as an event and chronic pancreatitis as a process that is sequentially linked to AP and reflects a complex interaction between genetic and environmental factors [7]. The major common genetic risk factors have yet to be defined [8].

The renin-angiotensin system (RAS) has been investigated in the pathogenesis of several diseases. Local RAS components exist in brain, heart, kidney, pancreas, adrenal glands and gonads [9-11], and contribute in the regulation of cell growth, differentiation, proliferation and apoptosis, reactive oxygen species generation, tissue inflammation and fibrosis, and hormonal secretion [12]. Renin-angio-tensin system has been implicated in pathogenesis

of AP and chronic pancreatitis [8]. Although the etiology of AP is believed to be multifactorial, the activation of proteolytic enzymes, lipase, kinins and other active peptides may be responsible for alterations of RAS expression [13,14]. In fact, the activity of the plasma RAS is significantly increased in AP [15,16]. Renin-angiotensin system is important in regulation of electrolyte balance, fluid and blood pressure. Angiotensin-converting enzyme is the key enzyme which activates the RAS [8,9] by converting angiotensin I to angiotensin II, which is a potent vasoconstrictor. The ACE inactivates bradykinin, a vasodilator of the kallikrein-kinin system, which has major influence in inflammatory processes. Since angiotensinogen and angiotensin receptors may play a role in induction of inflammation and mi-crocirculatory regulation in the pancreas, they may contribute to its injury in AP [16,17]. Association of severe AP and impairment of pancreatic micro-circulation has been demonstrated in experimental models of AP [18]. Indeed, vasoconstriction, capillary stasis, decreased oxygen tension, and progressive ischemia occur early in the course of AP [19].

The ACE gene is located on human chromosome 17q23. Three genotypes are associated with an Alu repetitive sequence about 287 bp long on in-tron 16. These genotypes are insertion (I) and deletion (D) alleles, respectively [16,17].

The DD genotype has been linked to several inflammatory diseases [8,9] and results in higher levels of circulating ACE than the II and DI genotypes. It is also significantly more frequent in patients with myocardial infarction or diabetic proteinuria than in controls [10]. However, several studies have reported that the ACE I/D polymorphism was not a risk factor in AP and chronic pancreatitis [8,9]. In this study, we investigated the I/D polymorphism in AP.