HELICOBACTER PYLORI SEROPREVALENCE AND ITS ASSOCIATION WITH THE EPIGENOME, HYPERTENSION, AND TYPE 2 DIABETES MELLITUS

Background: Helicobacter pylori (H. pylori), common enteric Gram-negative bacterium, infection may lead to systemic inflammation, which increases the risk of hypertension (HTN) and type 2 diabetes mellitus (T2D). Studies between chronic H. pylori infection and cardiometabolic disorders have yielded mixed results and tend to be cross-sectional and conducted in older adults. They also do not address possible epigenetic mechanisms. The aims of this dissertation are to (1) quantify the association between H. pylori seropositivity and blood pressure (BP) and hemoglobin A1c (HbA1c) at two time points, and (2) determine if H. pylori infection is associated with changes in DNA methylation (DNAm), particularly at probes associated with cardiometabolic disorders.Methods: Aim 1 examines the cross-sectional and longitudinal associations between immunoglobulin G antibodies to H. pylori and BP and HbA1c across 10 years of follow-up in 5019 participants from the National Longitudinal Study of Adolescent to Adult Health (Add Health). Aim 2 uses DNAm data collected at follow-up to perform an epigenome-wide association study (EWAS) and identify if any differentially methylated cytosine-phosphate-guanine (CpG) probes associated with H. pylori infection are also linked to cardiometabolic markers. EWAS analyses were repeated in two other chronic pathogens, cytomegalovirus (CMV) and Herpes simplex virus-1, to determine if differentially methylated CpG probes were associated with H. pylori infection or general inflammation.Results: In Aim 1, H. pylori seroprevalence was associated with a decrease in mean systolic BP cross-sectionally. However, H. pylori seroprevalence was not associated with diastolic BP, HbA1c, prevalent or incident HTN, or T2D. In Aim 2, five differentially methylated CpG probes were associated with H. pylori seroprevalence, including one annotated to WDR27, a gene related to glycemic load. One CpG probe associated with H. pylori seroprevalence was also associated with CMV, and two annotated genes were associated with CMV at different CpG probes.Conclusions: Aim 1 supported studies that have not found an association between H. pylori and HTN and T2D. Still, H. pylori infection may be connected to cardiometabolic disorders through changes in DNAm. This project highlights the complexity by which chronic pathogens may prime the body for future chronic disorders.