Genetic Susceptibility of Gastroduodenal Disease in Ethnic and Regional Diversity

Helicobacter pylori is a human pathogen that infects the stomach. More than half of the human population is infected with H. pylori, which is major cause of peptic ulcers, gastric cancers and mucosa-associated lymphoid tissue lymphoma. However, the majority of patients infected with H. pylori generally remain asymptomatic and never develop significant disease. H. pylori has high genetic diversity, and different genotypes of H. pylori are involved in different gastroduodenal disorders. The hosts’ genetic factors also influence the development of peptic ulcers and gastric cancer, and plenty of evidence has demonstrated that genetics plays a role in susceptibility and contributes to the differences between those who develop H. pylori infection, peptic ulcers and gastric cancer. Numerous single nucleotide polymorphism (SNP) studies have been undertaken to identify candidate genes that most likely play a role in the development of peptic ulcers and gastric cancer. Recently, a genome wide association study (GWAS) and next generation sequencing study identified several genetic loci that confer susceptibility for H. pylori infection and gastroduodenal disease. H. pylori prevalence is as high as 90% in some countries, but approximately 5% to 10% of a given population is never infected with H. pylori, even in the presence of high exposure rates. A GWAS meta-analysis identified an association between Toll-like receptor 1 (TLR1) and H. pylori seroprevalence, suggesting that genetic variations in TLR1 may explain some of the observed variations in individual risk for developing H. pylori infection. The pathogenesis of different clinical outcomes is multifactorial and includes the virulence of H. pylori, environmental