title: A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections.
abstract: This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfortunately, only a few functional SNPs have been identified. The candidate gene approach can be seen as a useful first step in exploring causal pathways between genetic determinants and complex diseases such as those mentioned above. To date, little is known about the immunogenetics of upper gastrointestinal tract diseases. We review the literature on H. pylori, EBV and gene polymorphisms that affect key immune mediators influencing the pathogenesis of the inflammatory response, such as the genes that code for the IL-1 family, TNF-alpha, lymphotoxin alpha, and IL-10. IL-1, IL-10, lymphotoxin alpha and TNF-alpha polymorphisms increase the risk of upper gastrointestinal pathogenesis in H. pylori-infected patients, whereas IL-1 and TNF-alpha polymorphisms confer risk in EBV-infected patients.
authors.affiliation: Department of Gastroenterology, Laboratory of Immunogenetics VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Ouburg
authors.forename: J
authors.initials: J
authors.lastname: Bart A Crusius
authors.forename: Elly C
authors.initials: EC
authors.lastname: Klinkenberg-Knol
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: A
authors.initials: A
authors.lastname: Salvador Peña
authors.forename: Servaas A
authors.initials: SA
authors.lastname: Morré
mesh_terms: D016207:Cytokines / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000235:genetics; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000382:microbiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D007125:Immunogenetics; D007375:Interleukin-1 / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D016207:Cytokines; D007375:Interleukin-1