Helicobacter pylori is the major causative agent of numerous gastric disorders including gastric cancer, the second leading cause of cancer mortality worldwide. While over half of the world’s population are infected with the bacterium, only a small fraction of these individuals develop severe health outcomes. This acknowledgement suggests other factors, including host and pathogen genetic variation, genetic interactions, and environmental factors are likely to play an important role in the development of gastric disease after H. pylori infection. Recent research has sought to fill these gaps in knowledge, with one such study concluding that coevolution between humans and H. pylori is a likely modifier of disease risk.
To further explore the underlying contributors to gastric disorders, we examined the association between the severity of gastric lesions, quantified through histopathologic scores, and patterns of genomic variation in matched human and H. pylori samples. Analyzed data were obtained from a previous study, with study participants having been recruited from two distinct Colombian populations possessing significantly different incidences of gastric cancer but similar H. pylori infection prevalence. Estimates of human ancestry, polymorphisms in human immunogenes, H. pylori ancestry, and three Helicobacter virulence factors (CagA, VacAs, and VacAm) were utilized for study. Pairwise interactions between matched human polymorphisms and H. pylori ancestry, as well as H. pylori virulence factors and human ancestry, were examined for risk of increased gastric disease severity using multifactor dimensionality reduction (MDR).
Though no statistically significant interactions between H. pylori virulence factors and human ancestry were found, this study identified potentially significant interactions between polymorphisms in human immunogenes and H. pylori ancestry. These interactions likely have biological relevance. The findings of this study have numerous potential implications. First, the approach used in this analysis was novel and may serve as a guide to researchers in other fields and for other topics. The research also furthers the knowledge and study of H. pylori infection and gastric outcomes. Importantly, this study analyzed genetic interactions, an often overlooked determinant of disease, in a novel way, with ancestry as a potential explanatory variable. The interactions found in this study will need further validation in larger studies. However, this study and the genetic interactions found have numerous potential benefits, including new knowledge of genetic risk factors of gastric disease severity. This knowledge can be used to develop better models for prediction of gastric disease which would have large implications for epidemiology, genetics, and the risk assessment or treatment of gastric conditions.