In Program Announcement PA-06-183: """"""""HEALTH DISPARITIES IN NIDDK DISEASES,"""""""" The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) seeks research to understand and mitigate issues of health disparities in high priority diseases within its scope, including Helicobacter pylori infection, which infects 62% of Hispanics compared to 26% in non-Hispanic whites. Persistent H. pylori infection is associated with more than 50% of peptic ulcers and is a strong risk factor for stomach cancer. Our objective is to identify genetic and environmental factors that influence acquisition and persistence of H. pylori infection in Hispanic children. We will use PASITOS (NIDDK R01-DK53664), a birth cohort of low income Hispanic children on the US-Mexico border which was established to investigate the natural history of H. pylori infection. PASITOS demonstrated that most H. pylori infections acquired early in life do not persist: so, genetic risk factors may determine infection persistence, possibly in combination with environmental factors. Recent studies have shown that the immune response plays a role in susceptibility to H. pylori infection. The toll-like receptor (TLR) signal transduction pathway regulates immune response to gram negative bacteria with flagella, including H. pylori. We hypothesize that H. pylori colonization and persistence are influenced by genetic variation in the TLR pathway as measured by single nucleotide polymorphisms (SNPs). Secondarily, we hypothesize that these same SNPs modify the effects of measures for bacterial load: that is, infection in the household. Understanding the role of genetic and environmental factors in the acquisition and persistence of H. pylori infection could help to identify subgroups that are highly susceptible to chronic H. pylori infection and determine potential molecular targets for intervention to prevent subsequent gastric disease.
Specific Aims are: 1) To determine if SNPs in the TLR signal transduction pathway influence the incidence and persistence of H. pylori infection. We will take collected samples and evaluate SNPs in the TLR signal transduction pathway. A Bayesian approach will be used to estimate SNP and epistatic effects on colonization and persistence. 2) To determine if SNPs that are associated with incidence and persistence of H. pylori infection modify the effects of environmental factors associated with infection risk: in particular, bacterial load as measured by household infection levels.
TO PUBLIC HEALTH: While H. pylori infection rates are high in low income Hispanic children, antibiotics might not be necessary to prevent stomach diseases linked to constant infection for some children. We need to find out who will develop constant infection and treat them. Since immune response and bacterial exposure influence infection, we propose to look at related genes and household infection and how they interact to predict H. pylori infection in the PASITOS study. ? ? ?