GENETIC DETERMINANTS AND CLINICO-PATHOLOGICAL OUTCOMES OF HELICOBACTER PYLORI INFECTION


A.O. Oluwasola

Department of Pathology, College of Medicine, University College Hospital, Ibadan, Nigeria.

Abstract

Helicobacter pylori is a spiral Gram-negative bacterium with a relatively small genome and is known to be the most common human bacterial infection worldwide, infecting about half of the world’s population. The bacterium represents one of the most successful human pathogens, inducing severe clinical symptoms only in a small subset of individuals, thus signifying a highly balanced degree of co-evolution of H. pylori and humans. The prevalence of Helicobacter pylori infection varies greatly among countries and among population groups within the same country, but is falling in most developed countries. The clinical course of H. pylori infection is highly variable and is influenced by both microbial and host factors including genetic susceptibility while the pattern and distribution of inflammation correlate strongly with the risk of clinical sequelae, namely duodenal or gastric ulcers, mucosal atrophy, gastric carcinoma, or gastric lymphoma. Cytokine gene polymorphisms directly influence inter-individual variation in the magnitude of cytokine response, and this clearly contributes to an individual’s ultimate clinical outcome. Polymorphisms in genes coding for innate immune factors have also been incriminated in the pathogenesis of H. pylori related disease, while promoter hypermethylation of tumor suppressor genes is considered an important factor in carcinogenesis and known to be present in H. pylori associated gastric tumors. Functional genomics may fill many of the gaps in our understanding of the pathogenesis of H. pylori infection and accelerate the development novel therapies, including H. pylori specific antimicrobial agents.

Keywords: Helicobacter pylori, Genetic Factors,Clinic-Pathological Outcomes

Correspondence:

Dr. A.O. Oluwasola
Department of Pathology,
College of Medicine,
University College Hospital,
Ibadan, Nigeria.

Introduction

Helicobacter pylori (H. pylori) is a spiral Gram-negative bacterium with a relatively small genome (~1.65 Mb), and is known to be the most common human bacterial infection worldwide, infecting about half of the world’s population. There is now much evidence that H. pylori and related Helicobacter species have been part of the normal microbiota of humans and our ancestors for millions, if not tens of millions, of years or longer.1,2

The prevalence of Helicobacter pylori infection varies greatly among countries and among population groups within the same country, but is falling in most developed countries3. In the last 30 years, since H. pylori was first described and cultured, a complete paradigm shift has occurred in the clinical approach to the diagnosis and treatment of upper gastro-duodenal disease. Peptic ulcer disease is now approached as an infectious disease, in which elimination of the causative agent cures the condition. The role of H. pylori infection in gastric cancers is increasingly recognized, and its role in other diseases of the upper gastrointestinal tract is being evaluated. Effective antimicrobial therapy is available, although there is still no ideal treatment, and indications for therapy continue to evolve.

Helicobacter pylori infection is usually acquired early in childhood but infection persists lifelong in the absence of treatment, and the majority (80%–90%) of those infected will carry and transmit H. pylori without any symptoms of disease. All strains cause gastric inflammation, however, only 15% of infections result in peptic ulceration and only 0.5%–2% in gastric adenocarcinoma.4 In some subjects, H. pylori is considered as a commensal and not a pathogen, making it difficult to determine who should be treated to prevent serious sequelae.5 Many clinical and basic research studies have been undertaken to define what makes H. pylori a pathogen. The clinical course of H. pylori infection is highly variable and is influenced by both microbial and host factors including genetic susceptibility. The pattern and distribution of inflammation correlate strongly with the risk of clinical sequelae, namely duodenal or gastric ulcers, mucosal atrophy, gastric carcinoma, or gastric lymphoma.

There has been recent interest in whether H. pylori may cause or be a risk factor for human diseases outside the upper gastrointestinal tract. These include idiopathic thrombocytopenic purpura, various skin diseases, liver diseases, cardiovascular and cerebrovascular disease.6 This review highlights recent advances in the understanding of genetic determinants of Helicobacter pylori infection as well as the interplay of clinical and morphological patterns in disease manifestation.