MITOCHONDRIA AND METABOLIC SYNDROME IN A SOUTHERN CALIFORNIA CHINESE COHORT
MITOCHONDRIA AND METABOLIC SYNDROME IN A SOUTHERN CALIFORNIA CHINESE COHORT
批准号:
8166909
负责人:
Douglas C Wallace
金额:
$3.88万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-12-01 至 2010-06-30
关键词:
AsiansCaliforniaChinese PeopleComputer Retrieval of Information on Scientific Projects DatabaseDefectDiabetes MellitusEtiologyExhibitsFamilyFundingGene RearrangementGenerationsGenetic PolymorphismGrantHaplogroupInstitutionInvestigationKnowledgeLaboratoriesMetabolic syndromeMitochondriaMitochondrial DNAMutationNon-Insulin-Dependent Diabetes MellitusOxidative PhosphorylationPlayPredispositionResearchResearch Ethics CommitteesResearch PersonnelResourcesRiskRoleSamplingSourceTaiwanTestingUnited States National Institutes of HealthVariantcase controlcohortdesignfallsgenetic pedigreemitochondrial DNA mutationmitochondrial dysfunctionsample collectiontransmission process
中文摘要
该子项目是利用
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得主要资金,
因此可以在其他CRISP条目中表示。列出的机构是
中心,不一定是研究者的机构。
自13年前我们实验室首次将2型糖尿病与一个三代母系家系的mtDNA重排联系起来以来,越来越多的人支持我们的假设,即线粒体功能障碍在2型糖尿病(DM)和重叠代谢综合征(MS)的病因学中起重要作用。通过这项研究,我们计划通过广泛调查线粒体DNA(mtDNA)中有害序列变异可能引起的线粒体氧化磷酸化(OXPHOS)缺陷,来大幅扩展该领域的现有知识。 这些致糖尿病的mtDNA变异体的范围从最近的、相对严重的、导致家族性DM & MS的大量OXPHOS缺陷的突变到古老的、相对温和的、导致部分OXPHOS缺陷和发展DM & MS风险增加的多态性。
为了验证这一假设,我们建议分析一个现有的收集样本从台湾华人家庭,表现出母亲传播的DM和MS以及约500台湾华人DM/MS非家族性病例和对照,以确定致病性mtDNA突变。该研究旨在寻找常见的亚洲mtDNA谱系(单倍型群)与MS和DM易感性之间的关联。台湾样本队列将不包括在本IRB申请中,但将属于已提交给研究审查委员会的单独豁免状态申请。(申请于2005年1月11日提交)。
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Since our laboratory's initial linkage of Type 2 diabetes to a mtDNA rearrangement in a three generation maternal pedigree 13 years ago, there has been increasing support for our hypothesis that mitochondrial dysfunction plays an important role in the etiology of Type 2 Diabetes Mellitus (DM) and the overlapping Metabolic Syndrome (MS). With this study we are planning to substantially expand upon the existing knowledge in the field by an extensive investigation of defects in mitochondrial oxidative phosphorylation (OXPHOS) caused potentially by deleterious sequence variants in the mitochondrial DNA (mtDNA). These diabetogenic mtDNA variants are proposed to range from recent, relatively severe, mutations resulting in substantial OXPHOS defects with familial DM & MS to ancient, relatively mild, polymorphisms that result in partial OXPHOS defects and an increase in the risk to develop DM & MS.
To test this hypothesis, we propose to analyze the mtDNAs of an existing collection of samples from Taiwan Chinese families, which exhibit maternal transmission of DM & MS as well as approximately 500 Taiwan Chinese DM/MS non familial cases and controls to identify causal pathogenic mtDNA mutations. The study is designed to look for associations between the common Asian mtDNA lineages (haplogroups) and predisposition to MS and DM. The Taiwanese cohort of samples will not be included under this IRB application but will fall under a separate, exempt status application which has been submitted to the Investigational Review Board. (application submitted 11/01/05).
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科研奖励(0)
会议论文
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批准号:10426606
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财政年份:2022
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资助金额:$83.08万
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Anti-tumor immunity and intestinal microbiota are modulated by mitochondrial DNA
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资助金额:$62.18万
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财政年份:2022
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A MITOCHONDRIAL-INTERNEURONAL HYPOTHESIS OF AUTISM
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项目类别:
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资助金额:$60.6万
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财政年份:2016
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批准号:8166898
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资助金额:$0.31万
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批准号:8007475
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项目类别:
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资助金额:$10.0万
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财政年份:2009
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负责人:Douglas C Wallace
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依托单位:
A Mitochondrial Etiology of Autism
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批准号:7843063
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项目类别:
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资助金额:$59.79万
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财政年份:2009
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负责人:Douglas C Wallace
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依托单位:
A Mitochondrial Etiology of Autism
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批准号:7938974
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项目类别:
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资助金额:$65.78万
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财政年份:2009
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负责人:Douglas C Wallace
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依托单位:
MITOCHONDRIAL DISEASES
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批准号:7951031
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项目类别:
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资助金额:$0.91万
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财政年份:2008
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负责人:Douglas C Wallace
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依托单位:
MITOCHONDRIA AND METABOLIC SYNDROME IN A SOUTHERN CALIFORNIA CHINESE COHORT
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批准号:7951049
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项目类别:
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资助金额:$10.19万
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财政年份:2008
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负责人:Douglas C Wallace
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依托单位:
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项目类别:
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资助金额:$1.14万
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财政年份:2007
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负责人:Douglas C Wallace
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依托单位:
MITOCHONDRIAL DISEASES
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批准号:7724990
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项目类别:
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资助金额:$0.87万
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财政年份:2007
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负责人:Douglas C Wallace
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依托单位:
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负责人:Douglas C Wallace
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项目类别:
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资助金额:$35.41万
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财政年份:2006
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负责人:Douglas C Wallace
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依托单位:
MITOCHONDRIAL DISEASES
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批准号:7606617
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项目类别:
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资助金额:$0.93万
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财政年份:2006
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负责人:Douglas C Wallace
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依托单位:
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MITOCHONDRIAL VARIATION
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资助金额:$0.08万
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资助金额:$35.41万
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财政年份:2006
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负责人:Douglas C Wallace
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依托单位:
海外基金