Translational Research in Polycystic Ovary Syndrome

多囊卵巢综合症的转化研究

• 批准号: 7932579
• 负责人: JOHN E NESTLER
• 金额: $ 12.09万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932579
• 关键词: Translational; Research; Polycystic; Ovary; Syndrome

DESCRIPTION (provided by applicant) The aim of Virginia Commonwealth University's (VCU) competitive renewal application for a SCCPRIR is to continue the critical infrastructure, collaborations and synergy for clinical and translational research on the causes and treatment of infertility in the polycystic ovary syndrome (PCOS), which is the most common cause of anovulatory infertility in the U.S. The SCCPRIR is housed at VCU (Drs. John Nestler and Jerome Strauss) and the consortium is at Pennsylvania State University (Penn State; Dr. Richard Legro). The three Key Projects and the Pilot Project all focus on the contributions of insulin resistance and heredity to infertility in PCOS. Project I (Dr. Legro) will assess if genetic marker D19S884 identifies young girls at increased risk to develop PCOS, and the utility of this marker in identifying girls with premature pubarche who would respond to metformin to prevent progression to PCOS. Project II (Dr. Nestler) proposes a pharmacogenetic study to assess the impact of genotype variation of SNP_rs8111669 in gene STK11, or SNPs in other candidate genes identified by Project III, on ovulatory response to metformin. Correlating in vitro studies will determine the influence of SNP_rs9111699 genotype on metformin response in cultured human theca cells and hepatocytes. Continuing human genetic studies that have been pivotal in identifying a PCOS susceptibility gene (D19S884), Project III will find the determinants and identify the effects of this genetic marker. It will also investigate candidate genes for PCOS other than D19S884, and will extend the genetic analysis from PCOS (a qualitative trait) to PCOS-associated quantitative traits. The SCCPRIR will be supported by a strong Administrative Core that will coordinate research activities and provide centralized processing of samples, assays, recruitment, advertising, and other functions necessary for the successful operation of the SCCPRIR. This application for renewal of the SCCPRIR is particularly well timed given VCU's recent recruitment of a new Dean of the School of Medicine (Dr. Strauss) with new resources for support of research; commitment to research (in particular in Women's Health), establishment of a CTSA, and the NIH Roadmap; and demonstrated success in increasing NIH funding.

描述（由申请人提供）弗吉尼亚联邦大学（VCU）的SCCPRIR竞争性续期申请的目的是继续对多囊卵巢综合征（PCOS）不孕症的原因和治疗进行临床和转化研究的关键基础设施，合作和协同作用，这是美国无排卵性不孕症最常见的原因。SCCPRIR位于VCU（John Nestler和杰罗姆施特劳斯博士），该财团位于宾夕法尼亚州立大学（宾夕法尼亚州立大学; Richard Legro博士）。三个重点项目和试点项目都集中在胰岛素抵抗和遗传对PCOS不孕症的贡献。项目I（Legro博士）将评估遗传标记D19 S884是否能识别出患有PCOS的风险增加的年轻女孩，以及该标记在识别对二甲双胍有反应以防止进展为PCOS的过早阴毛形成女孩中的效用。项目II（Nestler博士）提出了一项药物遗传学研究，以评估基因STK 11中SNP_rs8111669的基因型变异或项目III确定的其他候选基因中的SNP对二甲双胍排卵反应的影响。相关体外研究将确定SNP_rs9111699基因型对培养的人卵泡膜细胞和肝细胞中二甲双胍应答的影响。继续进行人类遗传学研究，在确定PCOS易感基因（D19 S884）方面发挥了关键作用，项目III将找到决定因素并确定该遗传标记的影响。它还将研究D19 S884以外的PCOS候选基因，并将遗传分析从PCOS（一种定性性状）扩展到PCOS相关的定量性状。SCCPRIR将得到一个强大的行政核心的支持，该核心将协调研究活动，并提供样本的集中处理、分析、招募、广告和SCCPRIR成功运行所需的其他功能。鉴于弗吉尼亚大学最近招聘了一位新的医学院院长（Strauss博士），为研究提供新的资源;致力于研究（特别是妇女健康），建立CTSA和NIH路线图;并在增加NIH资金方面取得了成功，因此SCCPRIR的更新申请特别及时。