Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Digestion 2012;86:258–263 DOI: 10.1159/000341423 Secreted and Membrane-Bound Mucins and Idiopathic Peptic Ulcer Disease Yaron Niv Doron Boltin Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel Introduction The incidence of Helicobacter pylori and non-steroi- dal anti-inflammatory drug (NSAID) or aspirin-nega- tive peptic ulcer disease has increased steadily over the last two decades, especially in the USA and Western Eu- rope, and in countries where H. pylori infection rates are low or declining [1]. It has been proposed that the inci- dence of idiopathic peptic ulcer disease varies inversely with H. pylori infection rates in a given population [2]. This hypothesis has no rational basis and relies on math- ematical evaluations. In actual fact, in some high H. py- lori prevalence countries the rate of idiopathic peptic ul- cer disease is high, and in some countries with a low prevalence of H. pylori infection the rate of idiopathic peptic ulcer disease is low (table 1). For example, in Pak- istan and Japan, both high H. pylori prevalence coun- tries, the prevalence of H. pylori-negative/NSAID-nega- tive ulcers is 29 and 1.3%, respectively, indicating that there is not inverse variance with H. pylori prevalence (table 1) [3–9]. In two cohorts from Hong Kong, the prev- alence of H. pylori/NSAID-negative peptic ulcer ranged from 4.1% up to 17% [6, 10]. The prevalence of idiopathic peptic ulcer disease is probably influenced by a balance between protective and noxious factors, which may differ from one cohort to an- other. Although the definition of idiopathic peptic ulcer disease requires the exclusion of noxious factors, such as Key Words Peptic ulcer  Mucin  Aspirin  Helicobacter pylori Abstract The incidence of Helicobacter pylori and non-steroidal anti- inflammatory drug (NSAID)-negative peptic ulcer disease has increased over the last two decades, especially in the Western world and in countries with low H. pylori infection rates. Idiopathic peptic ulcer disease is a recently described entity which relates to peptic ulcers not caused by H. pylori, NSAID/aspirin therapy, other ulcerogenic organisms and drugs, or other rare malignant and benign diseases. Struc- tural and secreted mucins create the unstirred gastric mucus layer and maintain a stable pH above the gastric mucosa. This mucous layer prevents enzymatic attack by acid and pepsin. Inhibition of cyclooxygenase by NSAID and aspirin inhibits prostaglandin production, inhibits mucin and bicar- bonate secretion, and exposes the mucosa to the toxic ef- fects of acid and intragastric enzymes. There is also a com- plex relationship between H. pylori and different mucin sub- types which on one hand facilitates mucin invasion but on the other hand protects the gastric mucosa. Genetic and epi- genetic changes in the mucin molecule may be responsible for idiopathic peptic ulcer disease, but this hypothesis must be further investigated. Herein, the mucin hypothesis of id- iopathic peptic ulcer disease is explored. Copyright © 2012 S. Karger AG, Basel Published online: October 16, 2012 Prof. Yaron Niv Rabin Medical Center 39 Jabotinski Street Petach Tikva 49100 (Israel) Tel. +972 3 937 7237, E-Mail yniv  @  clalit.org.il © 2012 S. Karger AG, Basel 0012–2823/12/0863–0258$38.00/0 Accessible online at: www.karger.com/dig