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.

Epstein–Barr virus antibody level and gastric cancer risk in Korea: a nested case–control study

“…In this study, we measured seropositivity of H. pylori antibody and found that the interactions between seropositivity for H. pylori and EBV VCA IgG and EBNA IgG were not statistically significant (P ¼ 0.87 and P ¼ 0.79, respectively; data not shown). However, an interaction between both infections might be plausible, as both H. pylori and EBV infection have a role in carcinogenesis in the pathway of inflammation, chronic infection, and autoimmune pathway (Ouburg et al, 2005;Gwack et al, 2006). Several candidate gene approach studies suggest that EBNA genes interact with inflammatory and tumour suppressor genes, which has implications in gastric carcinogenesis (Ouburg et al, 2005).…”

“…However, an interaction between both infections might be plausible, as both H. pylori and EBV infection have a role in carcinogenesis in the pathway of inflammation, chronic infection, and autoimmune pathway (Ouburg et al, 2005;Gwack et al, 2006). Several candidate gene approach studies suggest that EBNA genes interact with inflammatory and tumour suppressor genes, which has implications in gastric carcinogenesis (Ouburg et al, 2005). In the analysis of EBNA, EA, and VCA antibodies, immunofluorescence assay methods are more time consuming and difficult to interpret, but are more specific, have high resolution, and stand as the 'gold standard' technique.…”

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

“…Because the ancestral parents are fully sequenced, the genotyped RI strains afford a powerful tool for identifying genes within QTLs and are particularly useful for mapping multiple and epistatic genetic effects underlying complex phenotypes, including those seen in infectious diseases. 22,47,[50][51][52] Among the different RI sets of mice, we found the BXD panel more suitable for us than other series (for example, the AXB set) as the BXD series is much larger, almost three-times more than used in any other series of experiments and because both parental strains (C57BL/ 6J and DBA/2J) have been fully sequenced, 30 and have been shown to differ in their response to many pathogens, 28,[53][54][55][56][57] …”

Joint effect between regular use of non-steroidal anti-inflammatory drugs, variants in inflammatory genes and risk of lymphoma

“…Inflammatory processes are in general a double-edged sword, they promote carcinogenesis, as has been shown for multiple cancer sites, but a sufficient expression of inflammatory cytokines is also of utmost importance for a functioning innate immune system. Several reports suggest a relevance of variants in IL1 genes in susceptibility to and clearance of infectious agents [66,67] as well as the progression of related diseases [68,69]. Viruses, namely EBV, HTLV-I, and HCV, and bacteria, such as Helicobacter pylori, play a significant role in an increasing number of lymphoma subtypes [5,70].…”