#METABOLOMICS WORKBENCH hormel101_20170623_091059 DATATRACK_ID:1077 STUDY_ID:ST000630 ANALYSIS_ID:AN000962 PROJECT_ID:PR000457
VERSION             	1
CREATED_ON             	June 25, 2017, 8:43 am
#PROJECT
PR:PROJECT_TITLE                 	Metabolomic Mechanisms of Dietary Salt Effects on Blood Pressure
PR:PROJECT_SUMMARY               	Enhanced sensitivity of blood pressure to salt intake is observed in
PR:PROJECT_SUMMARY               	approximately 50% of hypertensive patients, reaching 75% in African American
PR:PROJECT_SUMMARY               	hypertensive patients. We recently discovered a novel role of abnormal cellular
PR:PROJECT_SUMMARY               	intermediary metabolism in hypertension in the Dahl salt-sensitive (SS) rat, the
PR:PROJECT_SUMMARY               	most commonly used polygenic, hereditary model of human salt-sensitive
PR:PROJECT_SUMMARY               	hypertension. We propose to test the hypothesis that blood pressure sensitivity
PR:PROJECT_SUMMARY               	to dietary salt intake in human is associated with metabolite changes in the
PR:PROJECT_SUMMARY               	urine. Leveraging the expertise and resources at the Mayo Clinic Metabolomics
PR:PROJECT_SUMMARY               	Resources Core, we propose to perform targeted LC/MS analysis and NMR spectra
PR:PROJECT_SUMMARY               	generation in urine samples obtained from a subset of subjects from the Dietary
PR:PROJECT_SUMMARY               	Approaches to Stop Hypertension – Sodium (DASH2) clinical trial and kidney
PR:PROJECT_SUMMARY               	tissue extract and urine samples from SS rats and a newly generated transgenic
PR:PROJECT_SUMMARY               	rat that overexpresses fumarase (SS.Fh1+). The study will be the first to
PR:PROJECT_SUMMARY               	systematically characterize urinary metabolite profiles associated with blood
PR:PROJECT_SUMMARY               	pressure response to salt in humans. The study is anticipated to generate new
PR:PROJECT_SUMMARY               	insight into the mechanisms (particularly renal mechanisms) underlying
PR:PROJECT_SUMMARY               	salt-sensitive hypertension. Findings of the proposed study could lead to an
PR:PROJECT_SUMMARY               	expanded clinical study as well as mechanistic studies in animal models.
PR:INSTITUTE                     	Mayo Clinic
PR:LAST_NAME                     	Liang
PR:FIRST_NAME                    	Mingyu
PR:ADDRESS                       	Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
PR:EMAIL                         	mliang@mcw.edu
PR:PHONE                         	414-955-8539
#STUDY
ST:STUDY_TITLE                   	Neuromodulator Metabolites of Dietary Salt Effects on Blood Pressure in Human
ST:STUDY_TITLE                   	Urine from 20 Participants of the DASH2 Clinical Trial (part III)
ST:STUDY_SUMMARY                 	The objective of the study is to identify changes of urinary metabolite profiles
ST:STUDY_SUMMARY                 	associated with different responses to blood pressure to salt. Subjects are
ST:STUDY_SUMMARY                 	derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium
ST:STUDY_SUMMARY                 	Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med.
ST:STUDY_SUMMARY                 	2001).We choose two groups subjects who meet the following conditions(the two
ST:STUDY_SUMMARY                 	groups are separately named A and B). We chose subjects on the Control diet
ST:STUDY_SUMMARY                 	.These subjects meet the blood pressure criteria described below:Group A
ST:STUDY_SUMMARY                 	subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic
ST:STUDY_SUMMARY                 	blood pressure from the low sodium visit is less than 140 and the diastolic
ST:STUDY_SUMMARY                 	blood pressure from low sodium visit is less than 90; 3) For group A: Either the
ST:STUDY_SUMMARY                 	systolic blood pressure from the high sodium visit was greater than 10 mmHg
ST:STUDY_SUMMARY                 	higher than the systolic blood pressure from the low sodium visit, or the
ST:STUDY_SUMMARY                 	diastolic blood pressure from the high sodium visit was greater than 10 mmHg
ST:STUDY_SUMMARY                 	higher than the diastolic blood pressure from the low sodium visit; 3) For group
ST:STUDY_SUMMARY                 	B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e.
ST:STUDY_SUMMARY                 	+/- 5) from the systolic blood pressure from the low sodium visit, and the
ST:STUDY_SUMMARY                 	diastolic blood pressure from the high sodium visit is within 5 mmHg from the
ST:STUDY_SUMMARY                 	diastolic blood pressure from the low sodium visit. Use gas chromatography/mass
ST:STUDY_SUMMARY                 	spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry
ST:STUDY_SUMMARY                 	(LC/MS)analysis to find the differences of metabolic profiles between the high
ST:STUDY_SUMMARY                 	sodium level and the low sodium level, and compare the metabolic profiles of A
ST:STUDY_SUMMARY                 	with the metabolic profiles of B at the low and high sodium level. Note, this
ST:STUDY_SUMMARY                 	was used as a pilot, the rest of the samples are in another uploaded study.
ST:INSTITUTE                     	Mayo Clinic
ST:LAST_NAME                     	Liang
ST:FIRST_NAME                    	Mingyu
ST:ADDRESS                       	Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
ST:EMAIL                         	mliang@mcw.edu
ST:PHONE                         	414-955-8539
#SUBJECT
SU:SUBJECT_TYPE                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data
SUBJECT_SAMPLE_FACTORS           	DASH200367	ms5841-1	Sodium level:H | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200367	ms5841-2	Sodium level:L | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200298	ms5841-3	Sodium level:L | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200298	ms5841-4	Sodium level:H | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200052	ms5841-5	Sodium level:H | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200052	ms5841-6	Sodium level:L | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200136	ms5841-7	Sodium level:L | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200136	ms5841-8	Sodium level:H | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200035	ms5841-9	Sodium level:H | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200035	ms5841-10	Sodium level:L | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200125	ms5841-21	Sodium level:L | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200125	ms5841-22	Sodium level:H | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200161	ms5841-23	Sodium level:H | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200161	ms5841-24	Sodium level:L | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200218	ms5841-25	Sodium level:H | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200218	ms5841-26	Sodium level:L | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200238	ms5841-27	Sodium level:L | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200238	ms5841-28	Sodium level:H | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200167	ms5841-29	Sodium level:L | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200167	ms5841-30	Sodium level:H | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200050	ms5841-11	Sodium level:H | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200050	ms5841-12	Sodium level:L | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200064	ms5841-13	Sodium level:H | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200064	ms5841-14	Sodium level:L | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200100	ms5841-15	Sodium level:H | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200100	ms5841-16	Sodium level:L | grouping:A(salt sensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200375	ms5841-17	Sodium level:H | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200375	ms5841-18	Sodium level:L | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200060	ms5841-19	Sodium level:H | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200060	ms5841-20	Sodium level:L | grouping:A(salt sensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200199	ms5841-31	Sodium level:L | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200199	ms5841-32	Sodium level:H | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200306	ms5841-33	Sodium level:H | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200306	ms5841-34	Sodium level:L | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200193	ms5841-35	Sodium level:H | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200193	ms5841-36	Sodium level:L | grouping:B(salt insensitive)	gender=1
SUBJECT_SAMPLE_FACTORS           	DASH200244	ms5841-37	Sodium level:H | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200244	ms5841-38	Sodium level:L | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200389	ms5841-39	Sodium level:H | grouping:B(salt insensitive)	gender=2
SUBJECT_SAMPLE_FACTORS           	DASH200389	ms5841-40	Sodium level:L | grouping:B(salt insensitive)	gender=2
#COLLECTION
CO:COLLECTION_SUMMARY            	The urine samples we have were 24-hour collections occurring in the fourth week
CO:COLLECTION_SUMMARY            	on either the low- or the high-sodium intake level. In total, 120 human samples
CO:COLLECTION_SUMMARY            	(60 subjects, a low-sodium sample and a high-sodium sample for each subject)
CO:COLLECTION_SUMMARY            	will be analyzed.
#TREATMENT
TR:TREATMENT_SUMMARY             	We will analyze urine specimens collected during the Dietary Approaches to Stop
TR:TREATMENT_SUMMARY             	Hypertension – Sodium Study (DASH-Sodium or DASH2) clinical trial. More than
TR:TREATMENT_SUMMARY             	400 participants in the study were divided into two groups. One followed a
TR:TREATMENT_SUMMARY             	common Western diet, while the other group followed the “healthier” DASH
TR:TREATMENT_SUMMARY             	diet. Then each group had three 30 day periods, in random orders, that
TR:TREATMENT_SUMMARY             	corresponded to high, intermediate, or low sodium intakes while eating their
TR:TREATMENT_SUMMARY             	designated diet. The participants had all of their meals prepared and provided
TR:TREATMENT_SUMMARY             	for them during the entire study. It was found that reducing sodium intake
TR:TREATMENT_SUMMARY             	significantly reduced blood pressure especially when on the common Western diet.
TR:TREATMENT_SUMMARY             	We have obtained urine samples and phenotypic data for a subset of the
TR:TREATMENT_SUMMARY             	participants of the DASH2 trial form the NHLBI biospecimen and data repository
TR:TREATMENT_SUMMARY             	BioLINCC. We selected two sub-groups of participants on the Western diet. Group
TR:TREATMENT_SUMMARY             	A (n=31) exhibited large (>12 mmHg) differences in systolic or diastolic
TR:TREATMENT_SUMMARY             	pressure between low- and high-sodium intakes (“salt-sensitive” group).
TR:TREATMENT_SUMMARY             	Group B (n=29) showed similar blood pressure (differences <5 mmHg for both
TR:TREATMENT_SUMMARY             	systolic and diastolic pressures) between low- and high-sodium intakes
TR:TREATMENT_SUMMARY             	(“saltinsensitive” group).
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	2 drops of 6 N HCl was added in every 8 ml urine samples when the 24 hour urine
SP:SAMPLEPREP_SUMMARY            	was collected. All urine samples were stored in -80℃ freezer.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Waters Acquity
CH:COLUMN_NAME                   	Waters Acquity BEH C18 (150 x 2.1mm, 1.7um)
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:MS_COMMENTS                   	-
MS:INSTRUMENT_NAME               	Thermo Quantum Ultra
MS:INSTRUMENT_TYPE               	Triple quadrupole
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS         	uM
MS_METABOLITE_DATA_START
Samples	ms5841-1	ms5841-2	ms5841-3	ms5841-4	ms5841-5	ms5841-6	ms5841-7	ms5841-8	ms5841-9	ms5841-10	ms5841-21	ms5841-22	ms5841-23	ms5841-24	ms5841-25	ms5841-26	ms5841-27	ms5841-28	ms5841-29	ms5841-30	ms5841-11	ms5841-12	ms5841-13	ms5841-14	ms5841-15	ms5841-16	ms5841-17	ms5841-18	ms5841-19	ms5841-20	ms5841-31	ms5841-32	ms5841-33	ms5841-34	ms5841-35	ms5841-36	ms5841-37	ms5841-38	ms5841-39	ms5841-40
Factors	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:H | grouping:A(salt sensitive)	Sodium level:L | grouping:A(salt sensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)	Sodium level:H | grouping:B(salt insensitive)	Sodium level:L | grouping:B(salt insensitive)
Acetylcholine	124.8	447.4	399.1	517.1	0.0	308.4	166.0	0.0	0.0	0.0	0.0	52.3	10.7	155.4	253.5	0.0	0.0	36.7	46.8	0.0	0.0	0.0	29.2	0.0	15.0	6.1	13.8	14.1	101.5	62.4	9.7	6.8	0.0	0.0	4.4	4.5	20.2	3.8	103.5	0.0
Adenosine	64.5	234.0	87.5	132.4	0.0	114.3	29.3	0.0	0.0	0.0	0.0	1.8	1.6	7.8	69.7	39.0	0.0	5.8	1.6	0.0	0.0	0.0	87.2	0.0	17.1	5.2	18.2	13.5	106.0	96.6	8.3	6.6	0.0	0.0	6.3	4.8	4.8	3.2	9.2	0.0
Norepinephrine	0.2	0.5	0.2	0.0	0.1	0.8	0.4	0.1	0.1	0.0	0.1	0.2	0.1	0.3	0.3	0.1	0.0	0.3	0.2	0.0	0.0	0.0	0.6	0.0	0.3	0.2	0.9	0.7	0.0	0.5	0.2	0.1	0.0	1.0	0.1	0.2	0.4	0.2	0.3	0.0
Dopamine	0.8	1.9	0.3	0.3	0.2	2.6	1.6	0.1	0.3	0.0	0.4	1.2	0.6	1.0	1.6	0.0	0.0	1.1	0.6	0.0	0.0	0.0	2.8	0.5	1.1	0.9	1.5	1.2	0.0	2.2	0.8	0.5	0.0	3.1	0.5	0.5	3.1	1.5	2.1	4.0
Serotonin	1.2	0.0	0.0	0.0	0.0	0.0	2.6	0.0	0.0	0.0	0.0	1.5	0.5	0.5	1.5	2.3	0.0	0.5	0.5	0.0	0.0	0.0	1.4	0.0	1.1	0.8	0.0	0.5	0.0	1.9	0.3	0.8	0.0	0.0	0.6	0.3	1.8	1.6	44.4	0.0
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
Acetylcholine
Adenosine
Norepinephrine
Dopamine
Serotonin
METABOLITES_END
#END