Researchers Examine the Genetics Behind H. pylori Susceptibility

The authors of “Identification of Genetic Loci Associated with Helicobacter pylori Serologic Status,” published in the May 8 issue of JAMA, conducted two independent genome-wide association studies (GWASs) and a subsequent meta-analysis for anti-H pylori immunoglobulin G (IgG) serology. They reported that, of 10, 938 participants, 6,160 (56.3%) were seropositive for H pylori. The two GWASs identified the toll-like receptor (TLR) locus and the FCGR2A locus as being associated with H pylori seroprevalence.

According to a news release accompanying the publication of the article, the authors wrote “At this time, the clinical implications of the current findings are unknown. Based on these data, genetic testing to evaluate H pylori susceptibility outside of research projects would be premature… if confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H pylori infection.”

These findings could have important clinical implications, given that H pylori is a major cause of gastritis and gastroduodenal ulcer disease and is the only bacterial pathogen believed to cause cancer. H pylori prevalence is as high as 90% in some developing countries, but, the authors note, “10% of a given population is never colonized, regardless of exposure.”

The author of an accompanying editorial titled “Helicobacter pylori Susceptibility in the GWAS Era,” also published in the May 8 issue of JAMA, wrote that this study “provides novel and important data.” The data revealed that “lower expression of TLR1 (an innate immune response protein receptor) correlated with protection against H pylori infection, and higher expression correlated with increased likelihood of H pylori seropositivity and fecal antigen load.” This basically means that “too much TLR1 appears disadvantageous and increases the likelihood of acquiring or retaining the infection, provided there was exposure to begin with.”

Although the results from this study make genetic testing to evaluate H pylori susceptibility “premature,” according to the editorial, it is still important that we learn more about genetic susceptibility to H pylori because that is the key to understanding how to overcome this infection. The current approach to eradication of the infection “is limited and based entirely on prescribing a cocktail of antibiotics with an acid inhibitor to symptomatic individuals. However, H pylori antibiotic resistance is increasing steadily, and eventually curing even benign conditions such as peptic ulcer disease arising from H pylori will be difficult. When considering gastric cancer, another H pylori-induced global killer, the necessity for understanding the pathogenesis of the infection and the role of host genetics in susceptibility is even greater. The corollary is that better understanding of infections, including genetic epidemiology, is crucial to design measures to eradicate the downstream consequences of H pylori in large populations.”