Translational Study on the Regulation of Adenosylmethionine Synthesis During Chronic Inflammation
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 250
- Primary Endpoint
- s-adenosylmethionine
Study Overview
Brief Summary
The investigators propose to conduct a translational study on the regulation of S-adenosylmethionine synthesis and cellular methylation reactions during chronic inflammation. Development of in vitro cell models may reveal the regulatory mechanisms by which specific inflammatory mediators cause metabolic changes and alter DNA methylation status. Metabolic and pharmacological studies in the in vivo models will enable us to better understand the regulation of inter-organ homeostasis of S-adenosyl methionine and help identify tissue specific biomarkers for methylation and epigenetic modifications in different stage of chronic inflammation. The clinical study in human subjects will help distinguish the impacts of autoimmune rheumatic disease, degenerated joint disease, or specific medication use on significant clinical and biochemical markers in folate and vitamin B6 metabolic pathways.The Investigators hope the present study can identify specific clinical markers for potential epigenetic changes in patients suffering from chronic inflammation, which will contribute to better clinical management of these diseases in humans.
Detailed Description
The significance of epigenetic alterations in autoimmune rheumatic diseases and degenerated joint diseases has drawn great attention among clinicians and researchers. Aberrant methylation status has been demonstrated in human chronic inflammation yet more efforts have focused on global and sequence-specific hypomethylation and overexpression of specific genes. Few studies investigated the regulation of S-adenosylmethionine homeostasis and regulation during inflammation. At present the relevance and regulation of the complex epigenetic profiles and their modifications among different tissues and organs during inflammation remain largely unknown.
Study Design
- Study Type
- Observational
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •> 18 years
Exclusion Criteria
- •pregnancy,
- •anemia (hemoglobin 10 mg/dL or lower),
- •thrombocytopenia (platelet count below 50,000 cells/μL),
- •abnormal serum hepatic transaminase (aspartate aminotransferase or alanine aminotransferase above 50 IU/L),
- •diabetes or cancer
Outcomes
Primary Outcomes
s-adenosylmethionine
Time Frame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
blood samples were collected and stored for later analyses of above metabolites
homocysteine
Time Frame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
blood samples were collected and stored for later analyses of above metabolites
folate
Time Frame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
blood samples were collected and stored for later analyses of above metabolites
vitamin B6
Time Frame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
blood samples were collected and stored for later analyses of above metabolites
Secondary Outcomes
- blood amino acid profile (serine, glycine, methionine,cysteine, cystathionine, dimethylglycine)(Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor)
- polymorphisms in one carbon metabolism enzymes in PBMCs(Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor)
- gene expression of target enzymes in PBMCs(Blood were collected at admission.Blood were dawn again 1mo later if his medication was changed by the doctor)
- enzyme activities of S-adenosylmethionine synthase in RBC(Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor)
- vitamin B6 metabolic enzyme in RBC(Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor)
Investigators
En-Pei Isabel Chiang
Professor
National Chung Hsing University