Antihypertensive Drug/Gene Interactions And Cv Events View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

1991-2007

FUNDING AMOUNT

2954147 USD

ABSTRACT

Over the centuries, large numbers of polymorphisms in drug receptors, drug effector pathways, and other proteins developed. Some variant alleles have prospered in the absence of exposures to modern medications. With the epidemic of exposure to pharmacologically-active licit drugs of many classes, gene-drug interactions are likely to be a fruitful area of research in the application of molecular biology to public health. The focus of this revised competing-continuation application is hypertension. Pilot data were used to select drug-gene interactions for study. The primary aims are to assess drug-gene interactions on the incidence of myocardial infarction and stroke for (1) the alpha adducin polymorphism and diuretic use; (2) the beta-2 adrenergic receptor-27 (B2AR27) polymorphism and beta-blockers; and (3) the ACE insertion/deletion polymorphism and the ACE inhibitor use. Secondary aims include other potential gene-drug interactions with the G-protein beta-3 subunit (GB3) polymorphism, B2AR-16 polymorphism, the amiloride-sensitive epithelial sodium channel, and the angiotensinogen Met235Thr polymorphism. A tertiary aim is to use DNA extracted from surgical or pathological specimens to assess genotypes in fatal cases. This project is responsive to PA-99-016 since one aim is to identify genes that cause variation in drug response. The setting is Group Health Cooperative (GHC). GHC computerized files will be used to identify all treated hypertensive patients, aged 30 to 79 years, with incident MI or stroke during 1/1995 - 1/2004. Population-based controls with treated hypertension will be sampled from the GHC enrollment files. Data collection will include review of the ambulatory medical record, telephone interviews of consenting cases and controls, and the collection of venous blood specimen. Standard methods will be used to extract DNA and assay variant alleles. The GHC computerized pharmacy records will serve as the primary source of information about the use of antihypertensive medication. Frequency matching will control for the potential confounding effects of age, gender and year of presentation, and data analysis will involve restriction, stratification, and logistic regression. Case-control and case-only analyses are planned. Collecting data for an additional 5 years will identify 380 stroke cases, 760 MI cases and an additional 2,280 controls. For the alpha-adducin-diuretic interaction, for instance, this study will have 88 percent power to detect a multiplicative synergy index of 0.58 (the difference between an odds ratio of 0.46 and 0.79 in subjects with and without the variant, respectively). Power for other primary aims is excellent; power for secondary aims is good to excellent. More... »

URL

http://projectreporter.nih.gov/project_info_description.cfm?aid=6785306

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/2211", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "type": "DefinedTerm"
      }
    ], 
    "amount": {
      "currency": "USD", 
      "type": "MonetaryAmount", 
      "value": "2954147"
    }, 
    "description": "Over the centuries, large numbers of polymorphisms in drug receptors, drug effector pathways, and other proteins developed. Some variant alleles have prospered in the absence of exposures to modern medications. With the epidemic of exposure to pharmacologically-active licit drugs of many classes, gene-drug interactions are likely to be a fruitful area of research in the application of molecular biology to public health. The focus of this revised competing-continuation application is hypertension. Pilot data were used to select drug-gene interactions for study. The primary aims are to assess drug-gene interactions on the incidence of myocardial infarction and stroke for (1) the alpha adducin polymorphism and diuretic use; (2) the beta-2 adrenergic receptor-27 (B2AR27) polymorphism and beta-blockers; and (3) the ACE insertion/deletion polymorphism and the ACE inhibitor use. Secondary aims include other potential gene-drug interactions with the G-protein beta-3 subunit (GB3) polymorphism, B2AR-16 polymorphism, the amiloride-sensitive epithelial sodium channel, and the angiotensinogen Met235Thr polymorphism. A tertiary aim is to use DNA extracted from surgical or pathological specimens to assess genotypes in fatal cases. This project is responsive to PA-99-016 since one aim is to identify genes that cause variation in drug response. The setting is Group Health Cooperative (GHC). GHC computerized files will be used to identify all treated hypertensive patients, aged 30 to 79 years, with incident MI or stroke during 1/1995 - 1/2004. Population-based controls with treated hypertension will be sampled from the GHC enrollment files. Data collection will include review of the ambulatory medical record, telephone interviews of consenting cases and controls, and the collection of venous blood specimen. Standard methods will be used to extract DNA and assay variant alleles. The GHC computerized pharmacy records will serve as the primary source of information about the use of antihypertensive medication. Frequency matching will control for the potential confounding effects of age, gender and year of presentation, and data analysis will involve restriction, stratification, and logistic regression. Case-control and case-only analyses are planned. Collecting data for an additional 5 years will identify 380 stroke cases, 760 MI cases and an additional 2,280 controls. For the alpha-adducin-diuretic interaction, for instance, this study will have 88 percent power to detect a multiplicative synergy index of 0.58 (the difference between an odds ratio of 0.46 and 0.79 in subjects with and without the variant, respectively). Power for other primary aims is excellent; power for secondary aims is good to excellent.", 
    "endDate": "2007-08-31T00:00:00Z", 
    "funder": {
      "id": "https://www.grid.ac/institutes/grid.279885.9", 
      "type": "Organization"
    }, 
    "id": "sg:grant.2533412", 
    "identifier": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "2533412"
        ]
      }, 
      {
        "name": "nih_id", 
        "type": "PropertyValue", 
        "value": [
          "R01HL043201"
        ]
      }
    ], 
    "inLanguage": [
      "en"
    ], 
    "keywords": [
      "diuretic interaction", 
      "active licit drugs", 
      "diuretic use", 
      "B2AR-16 polymorphism", 
      "focus", 
      "absence", 
      "beta-blockers", 
      "many classes", 
      "potential", 
      "alpha adducin polymorphism", 
      "molecular biology", 
      "research", 
      "gene-drug interactions", 
      "CV EVENTS", 
      "exposure", 
      "other primary aims", 
      "data analysis", 
      "information", 
      "drug effector pathways", 
      "PA-99-016", 
      "large number", 
      "stratification", 
      "fruitful area", 
      "ACE insertion/deletion polymorphism", 
      "ANTIHYPERTENSIVE DRUG/GENE INTERACTIONS", 
      "hypertension", 
      "case-control", 
      "subjects", 
      "variants", 
      "genotypes", 
      "telephone interviews", 
      "logistic regression", 
      "drug response", 
      "data", 
      "frequency", 
      "variant alleles", 
      "instance", 
      "standard methods", 
      "case-only analysis", 
      "incident MI", 
      "use", 
      "hypertensive patients", 
      "incidence", 
      "power", 
      "sensitive epithelial sodium channel", 
      "public health", 
      "multiplicative synergy index", 
      "adrenergic receptor-27", 
      "Gb3", 
      "pharmacy records", 
      "primary source", 
      "century", 
      "other proteins", 
      "variation", 
      "GHC enrollment files", 
      "epidemic", 
      "pathological specimens", 
      "angiotensinogen Met235Thr polymorphism", 
      "genes", 
      "beta-3 subunit", 
      "population", 
      "polymorphism", 
      "venous blood specimens", 
      "restriction", 
      "modern medications", 
      "ambulatory medical record", 
      "DNA", 
      "years", 
      "cases", 
      "review", 
      "collection", 
      "Group Health Cooperative", 
      "secondary aim", 
      "odds ratio", 
      "percent power", 
      "alpha-adducin", 
      "application", 
      "myocardial infarction", 
      "assay variant alleles", 
      "data collection", 
      "effect", 
      "beta-2", 
      "gender", 
      "ACE inhibitor use", 
      "competing-continuation application", 
      "aim", 
      "differences", 
      "B2AR27", 
      "project", 
      "protein", 
      "presentation", 
      "GHC computerized files", 
      "SETTING", 
      "pilot data", 
      "antihypertensive medication", 
      "stroke cases", 
      "tertiary aim", 
      "control", 
      "age", 
      "fatal cases", 
      "drug receptors", 
      "MI cases", 
      "primary aim", 
      "study", 
      "drug-gene interactions", 
      "stroke", 
      "other potential gene-drug interactions"
    ], 
    "name": "ANTIHYPERTENSIVE DRUG/GENE INTERACTIONS AND CV EVENTS", 
    "recipient": [
      {
        "id": "https://www.grid.ac/institutes/grid.34477.33", 
        "type": "Organization"
      }, 
      {
        "affiliation": {
          "id": "https://www.grid.ac/institutes/grid.34477.33", 
          "name": "UNIVERSITY OF WASHINGTON", 
          "type": "Organization"
        }, 
        "familyName": "PSATY", 
        "givenName": "BRUCE M", 
        "id": "sg:person.0763727005.09", 
        "type": "Person"
      }, 
      {
        "member": "sg:person.0763727005.09", 
        "roleName": "PI", 
        "type": "Role"
      }
    ], 
    "sameAs": [
      "https://app.dimensions.ai/details/grant/grant.2533412"
    ], 
    "sdDataset": "grants", 
    "sdDatePublished": "2019-03-07T11:58", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com.uberresearch.data.processor/core_data/20181219_192338/projects/base/nih_projects_10.xml.gz", 
    "startDate": "1991-09-30T00:00:00Z", 
    "type": "MonetaryGrant", 
    "url": "http://projectreporter.nih.gov/project_info_description.cfm?aid=6785306"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/grant.2533412'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/grant.2533412'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/grant.2533412'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/grant.2533412'


 

This table displays all metadata directly associated to this object as RDF triples.

151 TRIPLES      19 PREDICATES      129 URIs      121 LITERALS      5 BLANK NODES

Subject Predicate Object
1 sg:grant.2533412 schema:about anzsrc-for:2211
2 schema:amount N5fd326d603bc4d898254781815a0d51d
3 schema:description Over the centuries, large numbers of polymorphisms in drug receptors, drug effector pathways, and other proteins developed. Some variant alleles have prospered in the absence of exposures to modern medications. With the epidemic of exposure to pharmacologically-active licit drugs of many classes, gene-drug interactions are likely to be a fruitful area of research in the application of molecular biology to public health. The focus of this revised competing-continuation application is hypertension. Pilot data were used to select drug-gene interactions for study. The primary aims are to assess drug-gene interactions on the incidence of myocardial infarction and stroke for (1) the alpha adducin polymorphism and diuretic use; (2) the beta-2 adrenergic receptor-27 (B2AR27) polymorphism and beta-blockers; and (3) the ACE insertion/deletion polymorphism and the ACE inhibitor use. Secondary aims include other potential gene-drug interactions with the G-protein beta-3 subunit (GB3) polymorphism, B2AR-16 polymorphism, the amiloride-sensitive epithelial sodium channel, and the angiotensinogen Met235Thr polymorphism. A tertiary aim is to use DNA extracted from surgical or pathological specimens to assess genotypes in fatal cases. This project is responsive to PA-99-016 since one aim is to identify genes that cause variation in drug response. The setting is Group Health Cooperative (GHC). GHC computerized files will be used to identify all treated hypertensive patients, aged 30 to 79 years, with incident MI or stroke during 1/1995 - 1/2004. Population-based controls with treated hypertension will be sampled from the GHC enrollment files. Data collection will include review of the ambulatory medical record, telephone interviews of consenting cases and controls, and the collection of venous blood specimen. Standard methods will be used to extract DNA and assay variant alleles. The GHC computerized pharmacy records will serve as the primary source of information about the use of antihypertensive medication. Frequency matching will control for the potential confounding effects of age, gender and year of presentation, and data analysis will involve restriction, stratification, and logistic regression. Case-control and case-only analyses are planned. Collecting data for an additional 5 years will identify 380 stroke cases, 760 MI cases and an additional 2,280 controls. For the alpha-adducin-diuretic interaction, for instance, this study will have 88 percent power to detect a multiplicative synergy index of 0.58 (the difference between an odds ratio of 0.46 and 0.79 in subjects with and without the variant, respectively). Power for other primary aims is excellent; power for secondary aims is good to excellent.
4 schema:endDate 2007-08-31T00:00:00Z
5 schema:funder https://www.grid.ac/institutes/grid.279885.9
6 schema:identifier N3129e1073d2e404196096f987650f982
7 N68bc1d525cb34443889e659a56129c00
8 schema:inLanguage en
9 schema:keywords ACE inhibitor use
10 ACE insertion/deletion polymorphism
11 ANTIHYPERTENSIVE DRUG/GENE INTERACTIONS
12 B2AR-16 polymorphism
13 B2AR27
14 CV EVENTS
15 DNA
16 GHC computerized files
17 GHC enrollment files
18 Gb3
19 Group Health Cooperative
20 MI cases
21 PA-99-016
22 SETTING
23 absence
24 active licit drugs
25 adrenergic receptor-27
26 age
27 aim
28 alpha adducin polymorphism
29 alpha-adducin
30 ambulatory medical record
31 angiotensinogen Met235Thr polymorphism
32 antihypertensive medication
33 application
34 assay variant alleles
35 beta-2
36 beta-3 subunit
37 beta-blockers
38 case-control
39 case-only analysis
40 cases
41 century
42 collection
43 competing-continuation application
44 control
45 data
46 data analysis
47 data collection
48 differences
49 diuretic interaction
50 diuretic use
51 drug effector pathways
52 drug receptors
53 drug response
54 drug-gene interactions
55 effect
56 epidemic
57 exposure
58 fatal cases
59 focus
60 frequency
61 fruitful area
62 gender
63 gene-drug interactions
64 genes
65 genotypes
66 hypertension
67 hypertensive patients
68 incidence
69 incident MI
70 information
71 instance
72 large number
73 logistic regression
74 many classes
75 modern medications
76 molecular biology
77 multiplicative synergy index
78 myocardial infarction
79 odds ratio
80 other potential gene-drug interactions
81 other primary aims
82 other proteins
83 pathological specimens
84 percent power
85 pharmacy records
86 pilot data
87 polymorphism
88 population
89 potential
90 power
91 presentation
92 primary aim
93 primary source
94 project
95 protein
96 public health
97 research
98 restriction
99 review
100 secondary aim
101 sensitive epithelial sodium channel
102 standard methods
103 stratification
104 stroke
105 stroke cases
106 study
107 subjects
108 telephone interviews
109 tertiary aim
110 use
111 variant alleles
112 variants
113 variation
114 venous blood specimens
115 years
116 schema:name ANTIHYPERTENSIVE DRUG/GENE INTERACTIONS AND CV EVENTS
117 schema:recipient Nd26ea99df99a4d7f99b3d48209692dab
118 sg:person.0763727005.09
119 https://www.grid.ac/institutes/grid.34477.33
120 schema:sameAs https://app.dimensions.ai/details/grant/grant.2533412
121 schema:sdDatePublished 2019-03-07T11:58
122 schema:sdLicense https://scigraph.springernature.com/explorer/license/
123 schema:sdPublisher N9ea9005c638442cbb4b7fa4c1fb9765a
124 schema:startDate 1991-09-30T00:00:00Z
125 schema:url http://projectreporter.nih.gov/project_info_description.cfm?aid=6785306
126 sgo:license sg:explorer/license/
127 sgo:sdDataset grants
128 rdf:type schema:MonetaryGrant
129 N3129e1073d2e404196096f987650f982 schema:name nih_id
130 schema:value R01HL043201
131 rdf:type schema:PropertyValue
132 N5fd326d603bc4d898254781815a0d51d schema:currency USD
133 schema:value 2954147
134 rdf:type schema:MonetaryAmount
135 N68bc1d525cb34443889e659a56129c00 schema:name dimensions_id
136 schema:value 2533412
137 rdf:type schema:PropertyValue
138 N9ea9005c638442cbb4b7fa4c1fb9765a schema:name Springer Nature - SN SciGraph project
139 rdf:type schema:Organization
140 Nd26ea99df99a4d7f99b3d48209692dab schema:member sg:person.0763727005.09
141 schema:roleName PI
142 rdf:type schema:Role
143 anzsrc-for:2211 schema:inDefinedTermSet anzsrc-for:
144 rdf:type schema:DefinedTerm
145 sg:person.0763727005.09 schema:affiliation https://www.grid.ac/institutes/grid.34477.33
146 schema:familyName PSATY
147 schema:givenName BRUCE M
148 rdf:type schema:Person
149 https://www.grid.ac/institutes/grid.279885.9 schema:Organization
150 https://www.grid.ac/institutes/grid.34477.33 schema:name UNIVERSITY OF WASHINGTON
151 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...