Pharmacogenetics of the Response to GLP-1 in Mexican-Americans with Prediabetes
患有糖尿病前期的墨西哥裔美国人对 GLP-1 反应的药物遗传学
基本信息
- 批准号:10448426
- 负责人:
- 金额:$ 68.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-09 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAdverse effectsAffectAftercareAgonistAlgorithmsAmericanBeta CellBloodBlood GlucoseBody Weight decreasedC-PeptideCandidate Disease GeneCardiovascular DiseasesCardiovascular systemCaucasiansChemosensitizationChronicChronic DiseaseClinicalClinical TrialsCollectionCommunitiesCountyDNA DatabasesDataDatabasesDiabetes MellitusDiabetes preventionDiseaseElectronic Health RecordEventGLP-I receptorGene ExpressionGene TargetingGenesGeneticGenetic ModelsGenetic studyGenomicsGenotypeGlucoseGoalsHealthHispanicHispanic PopulationsHormonesIndividualInsulinKidneyKidney DiseasesKnowledgeLatino PopulationLinkMeasurementMeasuresMetabolicMetabolic DiseasesMethodsMexicanMexican AmericansModelingMutationNon-Insulin-Dependent Diabetes MellitusObesityOralOutcomePathway interactionsPatientsPeripheralPersonsPharmaceutical PreparationsPharmacogeneticsPharmacogenomicsPharmacologic SubstancePharmacotherapyPhenotypePhysiologicalPlasmaPopulationPopulations at RiskPrecision therapeuticsPrediabetes syndromePreventionProceduresQuantitative Trait LociRegimenRegulationRenal functionRiskRisk ReductionRoleSingle Nucleotide PolymorphismStandardizationStatistical MethodsStructure of beta Cell of isletStudy SubjectTestingTherapeuticTissuesTranslatingTreatment FailureUnited StatesVariantWhole Bloodbasebiobankcardiovascular risk factorcohortcomorbiditydrug efficacyfunctional genomicsgene functiongenetic variantgenomic locusgenomic variationglucagon-like peptide 1improvedindexingindividual responseindividualized medicineinnovationinsulin secretioninsulin sensitivityinterestmeetingsnovelperipheral bloodpersonalized approachpersonalized therapeuticphenomeprecision geneticsprecision medicinepredicting responsepredictive modelingrecruitresponsetranscriptome sequencingtranscriptomicstreatment response
项目摘要
ABSTRACT
This clinical trial will uncover new mechanisms of inter-individual responses to endogenous and exogenous
glucagon-like peptide-1 (GLP-1) in Hispanics/Latinos (H/Ls) with prediabetes. The results move the
management of prediabetes, type 2 diabetes mellitus (T2DM), and relevant metabolic diseases to a more
individualized approach in an understudied and at-risk population. Few options exist for prediabetes treatment,
and the current pharmaceutical management of T2DM does not predict drug treatment failures, nor differences
in individual treatment responses and adverse effects. A precise, genetics-based approach will provide superior
therapeutic management for patients. GLP-1-based therapies reduce blood glucose, promote weight loss,
decrease cardiovascular events, and improve renal function. Prior genetic studies, most done in Caucasians,
identified associations between genetic variants and decreased GLP-1-induced insulin secretion, in an effort to
guide individualized treatment. However, these associations do not provide a clear mechanistic relationship
between genotype and phenotype. Transcriptomic analyses will uncover many of these mechanisms. Here, we
propose to 1) test the association of single nucleotide polymorphisms (SNPs) that regulate expression (eQTLs)
of 11 candidate genes in a range of relevant metabolic tissues with differential GLP-1 response, 2) perform RNA
sequencing before and after treatment to identify eQTLs in blood that predict response to GLP-1 therapy and
develop risk-based prediction models in H/Ls, and 3) determine the effects of genetic regulation of candidate
genes and newly discovered eQTLs phenome-wide in a large existing biobank, BioVU. For aims 1 and 2,
responses will be measured in 300 study subjects with prediabetes recruited from an established Mexican-
American cohort via the oral minimal model method, before and after GLP-1 therapy, quantifying GLP-1
hormone efficacy and GLP-1-induced pancreatic beta cell insulin release and peripheral insulin sensitivity.
Procedures include serial measurements of plasma glucose, insulin, C-peptide, and GLP-1, and peripheral blood
collection for RNA sequencing. Our central hypotheses are: (1) metabolic tissue-based eQTLs of GLP-1-
associated genes will be associated with physiological response to endogenous and exogenous GLP-1,
(2) identification of eQTLs associated with GLP-1 treatment-induced changes in whole blood will identify new
gene targets, and (3) this data will lead to the creation of eQTL-based prediction models for related diseases.
The study is innovative because it uses a novel combination of eQTL analysis and oral minimal model to assess
GLP-1 response, examines a population highly underrepresented in pharmacogenomic studies, and utilizes
novel statistical methods and applications to study gene expression. The significance of this newly acquired
mechanistic information will ultimately guide precision therapeutic regimens for diabetes prevention and
treatment, weight loss, cardiovascular risk reduction, and related metabolic complications in an understudied
population.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Absalon Dennis Gutierrez其他文献
Absalon Dennis Gutierrez的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Absalon Dennis Gutierrez', 18)}}的其他基金
Pharmacogenetics of the Response to GLP-1 in Mexican-Americans with Prediabetes
患有糖尿病前期的墨西哥裔美国人对 GLP-1 反应的药物遗传学
- 批准号:
10615867 - 财政年份:2021
- 资助金额:
$ 68.87万 - 项目类别:
Pharmacogenetics of the Response to GLP-1 in Mexican-Americans with Prediabetes
患有糖尿病前期的墨西哥裔美国人对 GLP-1 反应的药物遗传学
- 批准号:
10299488 - 财政年份:2021
- 资助金额:
$ 68.87万 - 项目类别:
GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
GLP-1 疗法:IL-6 信号传导和脂肪组织重塑在代谢反应中的作用
- 批准号:
9808679 - 财政年份:2019
- 资助金额:
$ 68.87万 - 项目类别:
GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
GLP-1 疗法:IL-6 信号传导和脂肪组织重塑在代谢反应中的作用
- 批准号:
10015259 - 财政年份:2019
- 资助金额:
$ 68.87万 - 项目类别:
GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
GLP-1 疗法:IL-6 信号传导和脂肪组织重塑在代谢反应中的作用
- 批准号:
10264099 - 财政年份:2019
- 资助金额:
$ 68.87万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 68.87万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 68.87万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 68.87万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 68.87万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 68.87万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 68.87万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 68.87万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 68.87万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 68.87万 - 项目类别:
Adverse Effects of Using Laser Diagnostics in High-Speed Compressible Flows
在高速可压缩流中使用激光诊断的不利影响
- 批准号:
RGPIN-2018-04753 - 财政年份:2022
- 资助金额:
$ 68.87万 - 项目类别:
Discovery Grants Program - Individual