{ "METABOLOMICS WORKBENCH":{"STUDY_ID":"ST000628","ANALYSIS_ID":"AN000960","VERSION":"1","CREATED_ON":"June 25, 2017, 8:27 am"}, "PROJECT":{"PROJECT_TITLE":"Metabolomic Mechanisms of Dietary Salt Effects on Blood Pressure","PROJECT_SUMMARY":"Enhanced sensitivity of blood pressure to salt intake is observed in approximately 50% of hypertensive patients, reaching 75% in African American hypertensive patients. We recently discovered a novel role of abnormal cellular intermediary metabolism in hypertension in the Dahl salt-sensitive (SS) rat, the most commonly used polygenic, hereditary model of human salt-sensitive hypertension. We propose to test the hypothesis that blood pressure sensitivity to dietary salt intake in human is associated with metabolite changes in the urine. Leveraging the expertise and resources at the Mayo Clinic Metabolomics Resources Core, we propose to perform targeted LC/MS analysis and NMR spectra generation in urine samples obtained from a subset of subjects from the Dietary Approaches to Stop Hypertension – Sodium (DASH2) clinical trial and kidney tissue extract and urine samples from SS rats and a newly generated transgenic rat that overexpresses fumarase (SS.Fh1+). The study will be the first to systematically characterize urinary metabolite profiles associated with blood pressure response to salt in humans. The study is anticipated to generate new insight into the mechanisms (particularly renal mechanisms) underlying salt-sensitive hypertension. Findings of the proposed study could lead to an expanded clinical study as well as mechanistic studies in animal models.","INSTITUTE":"Mayo Clinic","LAST_NAME":"Liang","FIRST_NAME":"Mingyu","ADDRESS":"Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226","EMAIL":"mliang@mcw.edu","PHONE":"414-955-8539"}, "STUDY":{"STUDY_TITLE":"TCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from 20 Participants of the DASH2 Clinical Trial","STUDY_SUMMARY":"The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level. Note, this was used as a pilot, the rest of the samples are in another uploaded study.","INSTITUTE":"Mayo Clinic","LAST_NAME":"Liang","FIRST_NAME":"Mingyu","ADDRESS":"Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226","EMAIL":"mliang@mcw.edu","PHONE":"414-955-8539"}, "SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"DASH200367", "Sample ID":"Sample #1", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200367", "Sample ID":"Sample #2", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200298", "Sample ID":"Sample #3", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200298", "Sample ID":"Sample #4", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200052", "Sample ID":"Sample #5", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200052", "Sample ID":"Sample #6", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200136", "Sample ID":"Sample #7", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200136", "Sample ID":"Sample #8", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200035", "Sample ID":"Sample #9", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200035", "Sample ID":"Sample #10", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200125", "Sample ID":"Sample #21", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200125", "Sample ID":"Sample #22", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200161", "Sample ID":"Sample #23", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200161", "Sample ID":"Sample #24", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200218", "Sample ID":"Sample #25", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200218", "Sample ID":"Sample #26", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200238", "Sample ID":"Sample #27", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200238", "Sample ID":"Sample #28", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200167", "Sample ID":"Sample #29", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200167", "Sample ID":"Sample #30", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200050", "Sample ID":"Sample #11", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200050", "Sample ID":"Sample #12", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200064", "Sample ID":"Sample #13", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200064", "Sample ID":"Sample #14", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200100", "Sample ID":"Sample #15", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200100", "Sample ID":"Sample #16", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200375", "Sample ID":"Sample #17", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200375", "Sample ID":"Sample #18", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200060", "Sample ID":"Sample #19", "Factors":{"Sodium level":"H","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200060", "Sample ID":"Sample #20", "Factors":{"Sodium level":"L","grouping":"A(salt sensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200199", "Sample ID":"Sample #31", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200199", "Sample ID":"Sample #32", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200306", "Sample ID":"Sample #33", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200306", "Sample ID":"Sample #34", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200193", "Sample ID":"Sample #35", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200193", "Sample ID":"Sample #36", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"1"} }, { "Subject ID":"DASH200244", "Sample ID":"Sample #37", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200244", "Sample ID":"Sample #38", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200389", "Sample ID":"Sample #39", "Factors":{"Sodium level":"H","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} }, { "Subject ID":"DASH200389", "Sample ID":"Sample #40", "Factors":{"Sodium level":"L","grouping":"B(salt insensitive)"}, "Additional sample data":{"gender":"2"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"The urine samples we have were 24-hour collections occurring in the fourth week on either the low- or the high-sodium intake level. In total, 120 human samples (60 subjects, a low-sodium sample and a high-sodium sample for each subject) will be analyzed."}, "TREATMENT":{"TREATMENT_SUMMARY":"We will analyze urine specimens collected during the Dietary Approaches to Stop Hypertension – Sodium Study (DASH-Sodium or DASH2) clinical trial. More than 400 participants in the study were divided into two groups. One followed a common Western diet, while the other group followed the “healthier” DASH diet. Then each group had three 30 day periods, in random orders, that corresponded to high, intermediate, or low sodium intakes while eating their designated diet. The participants had all of their meals prepared and provided for them during the entire study. It was found that reducing sodium intake significantly reduced blood pressure especially when on the common Western diet. We have obtained urine samples and phenotypic data for a subset of the participants of the DASH2 trial form the NHLBI biospecimen and data repository BioLINCC. We selected two sub-groups of participants on the Western diet. Group A (n=31) exhibited large (>12 mmHg) differences in systolic or diastolic pressure between low- and high-sodium intakes (“salt-sensitive” group). Group B (n=29) showed similar blood pressure (differences <5 mmHg for both systolic and diastolic pressures) between low- and high-sodium intakes (“saltinsensitive” group)."}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"2 drops of 6 N HCl was added in every 8 ml urine samples when the 24 hour urine was collected. All urine samples were stored in -80℃ freezer."}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"GC","INSTRUMENT_NAME":"Agilent 7890B","COLUMN_NAME":"Agilent HP5-MS (30m Ã— 0.25mm, 0.25 um)"}, "ANALYSIS":{"ANALYSIS_TYPE":"MS"}, "MS":{"MS_COMMENTS":"-","INSTRUMENT_NAME":"Agilent 5977A","INSTRUMENT_TYPE":"Single quadrupole","MS_TYPE":"EI","ION_MODE":"POSITIVE"}, "MS_METABOLITE_DATA":{ "Units":"uM", "Data":[{"Metabolite":"Lactate","Sample #1":"102.5","Sample #2":"96.8","Sample #3":"80.8","Sample #4":"60.4","Sample #5":"67.6","Sample #6":"76.9","Sample #7":"2010.9","Sample #8":"174.3","Sample #9":"65.9","Sample #10":"98.5","Sample #21":"82.8","Sample #22":"197.1","Sample #23":"146.4","Sample #24":"145.6","Sample #25":"180.5","Sample #26":"172.2","Sample #27":"88.0","Sample #28":"82.8","Sample #29":"235.1","Sample #30":"175.0","Sample #11":"67.8","Sample #12":"121.4","Sample #13":"45.4","Sample #14":"100.5","Sample #15":"79.4","Sample #16":"65.0","Sample #17":"253.9","Sample #18":"202.7","Sample #19":"90.6","Sample #20":"86.0","Sample #31":"33.5","Sample #32":"24.9","Sample #33":"72.9","Sample #34":"84.0","Sample #35":"346.2","Sample #36":"74.8","Sample #37":"496.2","Sample #38":"451.9","Sample #39":"212.7","Sample #40":"273.8"},{"Metabolite":"Succinate","Sample #1":"30.1","Sample #2":"17.0","Sample #3":"21.4","Sample #4":"13.9","Sample #5":"6.9","Sample #6":"10.1","Sample #7":"78.9","Sample #8":"57.1","Sample #9":"15.2","Sample #10":"19.3","Sample #21":"15.5","Sample #22":"860.0","Sample #23":"42.2","Sample #24":"38.6","Sample #25":"33.2","Sample #26":"1126.5","Sample #27":"13.7","Sample #28":"10.2","Sample #29":"218.9","Sample #30":"194.2","Sample #11":"15.8","Sample #12":"19.4","Sample #13":"64.0","Sample #14":"37.4","Sample #15":"51.8","Sample #16":"14.4","Sample #17":"10.9","Sample #18":"10.3","Sample #19":"18.8","Sample #20":"15.7","Sample #31":"4.6","Sample #32":"20.1","Sample #33":"24.4","Sample #34":"16.3","Sample #35":"6.4","Sample #36":"5.4","Sample #37":"198.7","Sample #38":"217.2","Sample #39":"18.2","Sample #40":"29.2"},{"Metabolite":"Fumarate","Sample #1":"8.7","Sample #2":"7.1","Sample #3":"7.1","Sample #4":"8.0","Sample #5":"5.6","Sample #6":"7.7","Sample #7":"17.4","Sample #8":"9.2","Sample #9":"8.1","Sample #10":"8.1","Sample #21":"5.3","Sample #22":"21.7","Sample #23":"11.5","Sample #24":"10.7","Sample #25":"7.4","Sample #26":"8.9","Sample #27":"5.5","Sample #28":"4.1","Sample #29":"10.9","Sample #30":"8.2","Sample #11":"6.0","Sample #12":"5.9","Sample #13":"4.8","Sample #14":"6.1","Sample #15":"8.7","Sample #16":"6.0","Sample #17":"6.1","Sample #18":"6.6","Sample #19":"8.5","Sample #20":"7.8","Sample #31":"2.8","Sample #32":"2.9","Sample #33":"11.9","Sample #34":"8.8","Sample #35":"7.9","Sample #36":"3.6","Sample #37":"3.4","Sample #38":"3.7","Sample #39":"6.2","Sample #40":"8.7"},{"Metabolite":"Oxaloacetate","Sample #1":"3.5","Sample #2":"3.5","Sample #3":"3.0","Sample #4":"2.0","Sample #5":"1.0","Sample #6":"1.6","Sample #7":"1.8","Sample #8":"1.4","Sample #9":"1.7","Sample #10":"2.4","Sample #21":"1.9","Sample #22":"0.9","Sample #23":"0.9","Sample #24":"0.9","Sample #25":"2.1","Sample #26":"0.5","Sample #27":"3.0","Sample #28":"0.7","Sample #29":"1.3","Sample #30":"1.9","Sample #11":"2.4","Sample #12":"4.7","Sample #13":"1.1","Sample #14":"1.5","Sample #15":"1.7","Sample #16":"0.9","Sample #17":"0.9","Sample #18":"0.9","Sample #19":"1.9","Sample #20":"1.1","Sample #31":"0.7","Sample #32":"0.4","Sample #33":"2.0","Sample #34":"1.3","Sample #35":"0.6","Sample #36":"0.4","Sample #37":"1.6","Sample #38":"0.5","Sample #39":"1.4","Sample #40":"2.0"},{"Metabolite":"Ketoglutarate","Sample #1":"128.3","Sample #2":"87.9","Sample #3":"64.7","Sample #4":"32.6","Sample #5":"17.5","Sample #6":"35.9","Sample #7":"316.2","Sample #8":"79.3","Sample #9":"59.1","Sample #10":"78.2","Sample #21":"65.3","Sample #22":"46.8","Sample #23":"62.2","Sample #24":"92.2","Sample #25":"117.6","Sample #26":"15.4","Sample #27":"18.9","Sample #28":"27.7","Sample #29":"62.0","Sample #30":"50.8","Sample #11":"22.0","Sample #12":"59.0","Sample #13":"42.8","Sample #14":"55.6","Sample #15":"89.0","Sample #16":"68.5","Sample #17":"44.0","Sample #18":"25.6","Sample #19":"101.3","Sample #20":"94.0","Sample #31":"13.6","Sample #32":"11.7","Sample #33":"20.9","Sample #34":"26.8","Sample #35":"41.5","Sample #36":"12.5","Sample #37":"167.0","Sample #38":"158.6","Sample #39":"61.5","Sample #40":"80.4"},{"Metabolite":"Malate","Sample #1":"9.0","Sample #2":"6.5","Sample #3":"5.4","Sample #4":"4.2","Sample #5":"4.4","Sample #6":"4.9","Sample #7":"29.2","Sample #8":"13.6","Sample #9":"14.2","Sample #10":"12.5","Sample #21":"5.0","Sample #22":"375.1","Sample #23":"14.0","Sample #24":"16.4","Sample #25":"7.6","Sample #26":"6.8","Sample #27":"130.0","Sample #28":"42.3","Sample #29":"15.3","Sample #30":"13.1","Sample #11":"7.5","Sample #12":"6.5","Sample #13":"6.4","Sample #14":"8.0","Sample #15":"5.4","Sample #16":"6.1","Sample #17":"8.3","Sample #18":"9.2","Sample #19":"8.1","Sample #20":"7.9","Sample #31":"3.2","Sample #32":"1.6","Sample #33":"10.4","Sample #34":"7.4","Sample #35":"12.1","Sample #36":"2.4","Sample #37":"18.6","Sample #38":"33.3","Sample #39":"7.7","Sample #40":"11.7"},{"Metabolite":"cis-Aconitic Acid","Sample #1":"280.9","Sample #2":"202.7","Sample #3":"166.1","Sample #4":"150.1","Sample #5":"101.1","Sample #6":"169.6","Sample #7":"200.6","Sample #8":"107.7","Sample #9":"72.7","Sample #10":"104.7","Sample #21":"130.3","Sample #22":"289.0","Sample #23":"79.4","Sample #24":"99.1","Sample #25":"139.7","Sample #26":"264.7","Sample #27":"96.4","Sample #28":"99.7","Sample #29":"170.1","Sample #30":"114.0","Sample #11":"147.8","Sample #12":"318.6","Sample #13":"109.4","Sample #14":"123.5","Sample #15":"169.4","Sample #16":"207.1","Sample #17":"87.8","Sample #18":"81.6","Sample #19":"168.4","Sample #20":"159.5","Sample #31":"59.6","Sample #32":"98.8","Sample #33":"204.9","Sample #34":"149.2","Sample #35":"101.2","Sample #36":"72.3","Sample #37":"100.5","Sample #38":"110.1","Sample #39":"104.9","Sample #40":"152.4"},{"Metabolite":"Citrate","Sample #1":"2551.1","Sample #2":"2186.5","Sample #3":"1152.6","Sample #4":"759.6","Sample #5":"263.6","Sample #6":"323.6","Sample #7":"4929.8","Sample #8":"3288.9","Sample #9":"2483.1","Sample #10":"4145.6","Sample #21":"2447.3","Sample #22":"237.0","Sample #23":"1852.8","Sample #24":"2265.8","Sample #25":"2589.8","Sample #26":"5043.9","Sample #27":"524.4","Sample #28":"595.8","Sample #29":"719.7","Sample #30":"964.6","Sample #11":"1103.0","Sample #12":"768.0","Sample #13":"1587.4","Sample #14":"1849.0","Sample #15":"1515.0","Sample #16":"464.9","Sample #17":"1676.2","Sample #18":"1799.3","Sample #19":"2693.2","Sample #20":"2629.6","Sample #31":"702.5","Sample #32":"425.6","Sample #33":"1550.9","Sample #34":"1114.8","Sample #35":"902.6","Sample #36":"532.3","Sample #37":"2408.4","Sample #38":"2020.9","Sample #39":"1713.5","Sample #40":"2479.4"},{"Metabolite":"Isocitrate","Sample #1":"374.1","Sample #2":"273.3","Sample #3":"235.5","Sample #4":"209.0","Sample #5":"141.1","Sample #6":"236.2","Sample #7":"228.6","Sample #8":"140.1","Sample #9":"115.6","Sample #10":"165.2","Sample #21":"181.7","Sample #22":"164.9","Sample #23":"103.0","Sample #24":"121.7","Sample #25":"223.2","Sample #26":"384.4","Sample #27":"119.1","Sample #28":"117.2","Sample #29":"223.7","Sample #30":"169.9","Sample #11":"183.4","Sample #12":"393.7","Sample #13":"132.6","Sample #14":"163.0","Sample #15":"220.6","Sample #16":"166.7","Sample #17":"105.6","Sample #18":"100.8","Sample #19":"208.0","Sample #20":"198.3","Sample #31":"72.8","Sample #32":"89.3","Sample #33":"259.2","Sample #34":"192.7","Sample #35":"102.3","Sample #36":"80.3","Sample #37":"128.9","Sample #38":"126.8","Sample #39":"126.7","Sample #40":"190.9"}], "Metabolites":[{"metabolite_name":"Lactate"},{"metabolite_name":"Succinate"},{"metabolite_name":"Fumarate"},{"metabolite_name":"Oxaloacetate"},{"metabolite_name":"Ketoglutarate"},{"metabolite_name":"Malate"},{"metabolite_name":"cis-Aconitic Acid"},{"metabolite_name":"Citrate"},{"metabolite_name":"Isocitrate"}] } }