Adenosylmethionine Metabolism in Human Inflammation

Translational Study on the Regulation of Adenosylmethionine Synthesis During Chronic Inflammation

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.

Study Overview

• Status: Unknown
• Conditions: Arthritis; Chronic Inflammation

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 Type: Observational
• Enrollment (Anticipated): 250

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients with arthritis or healthy adults

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Arthritis; subjects with arthritis
Health control subjects; Health control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
s-adenosylmethionine	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
homocysteine	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
folate	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
vitamin B6	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood amino acid profile (serine, glycine, methionine,cysteine, cystathionine, dimethylglycine)	blood samples were collected and stored for later analyses of above metabolites	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 samples were collected and stored for later analyses	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 samples were collected and stored for later analyses of above metabolites	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 samples were collected and stored for later analyses of above metabolites	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 samples were collected and stored for later analyses	Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor

Collaborators and Investigators

• Sponsor: National Chung Hsing University
• Collaborators: National Science Council, Taiwan; Ministry of Science and Technology, Taiwan
• Investigators: Principal Investigator: En-Pei I Chiang, PhD, Department of Food Science and Biotechnology, National Chung Hsing University

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: July 28, 2015
• First Submitted That Met QC Criteria: August 6, 2015
• First Posted (Estimate): August 11, 2015

Study Record Updates

• Last Update Posted (Estimate): August 11, 2015
• Last Update Submitted That Met QC Criteria: August 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: SF11093