Adenosylmethionine Metabolism in Human Inflammation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Translational Study on the Regulation of Adenosylmethionine Synthesis During Chronic Inflammation

Conditions
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Arthritis, Chronic Inflammation

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arthritis<br>subjects with arthritis | |
| Health control subjects<br>Health control | |

What is the study measuring?
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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 |