Balkan Journal of Medical Genetics

Gallstones are frequent in the Western world, with up to 10% of the general population affected. Gallstone prevalence is higher in the elderly and in women [1]. Most series indicate that the prevalence rate of gallstones in women between the ages of 20 and 55 years varies from 5 to 20%, and in those older than 50 years, from 25 to 30%. The prevalence rate in men is approximately one-half that in women for a given age group and the prevalence in children is 0.13% [2]. Acute cholangitis and pancreatitis are the most serious complications of gallstones, with considerable morbidity and mortality [1,3].

Acute cholangitis is an infectious disease of the biliary tract ranging in severity from a mild form with fever and jaundice to a severe form with septic shock. Patients are febrile, often have abdominal pain, and are jaundiced [4]. There is usually leukocy-tosis, and serum alkaline phosphatase and bilirubin levels are generally elevated [4,5]. Approximately 85% of cases are caused by an impacted stone in the common bile duct, with resulting bile stasis [6].

Acute pancreatitis is an acute inflammatory process with varied etiologies [7], but its pathogenesis is not fully understood [8]. Blockages of the duodenal papilla or ampulla of Vater are the common characteristics of the disease being most commonly due to gallstones, causing approximately 40% of cases [9]. Gallstone pancreatitis may be associated with cho-langitis but is also common as a separate entity [10]. A popular mechanism of gallstone pancreatitis is that an impacted gallstone in the distal common bile duct obstructs the pancreatic duct, increasing pancreatic pressure and damaging ductal and acinar cells [11].

Several studies have shown the existence of local renin-angiotensin system (RAS) components in brain, heart, kidney, pancreas, adrenal glands and gonads [12,13]. Local RAS functions include the regulation of cell growth, differentiation, proliferation and apoptosis, reactive oxygen species (ROS) generation, tissue inflammation and fibrosis, and hormonal secretion [14].

The systemic hormonal RAS regulates electrolyte balance, fluid and blood pressure. The angio-tensin-converting enzyme (ACE) is responsible for the conversion of angiotensin I to angiotensin II, which is a potent vasoconstrictor [15,16] and also inactivates bradykinin, a vasodilator produced by the kallikrein-kinin system, which has major implication in acute pancreatitis and other inflammations [17,18]. The ACE gene insertion/deletion (I/D) polymorphism is localized in intron 16 of the human ACE gene and corresponds to a repetitive sequence about 287 bp long [18,19].

In our clinical experience, some individuals with common bile duct stones are hospitalized more than once for treatment of biliary pancreatitis or for cho-langitis. Why do some of the people with common biliary duct stone suffer cholangitis, while others develop pancreatitis? The answer to this question is not yet quite clear. Angiotensin is a proinflammatory molecule and may have a role in cholangitis (an infectious disease) and pancreatitis (a sterile inflammation). To determine if the ACE genotype determines the occurrence of cholangitis or biliary pancreatitis, we studied patients with these diseases and healthy controls.