Translational Research in Polycystic Ovary Syndrome

说明(申请人提供)弗吉尼亚联邦大学(VCU)竞争续签SCCPRIR申请的目的是继续对多囊卵巢综合征(PCOS)不孕的原因和治疗进行关键的临床和翻译研究，SCCPRIR是美国最常见的无排卵性不孕原因。SCCPRIR位于VCU(John Nestler和Jerome Strauss博士)，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)。这三个重点项目和试点项目都集中在胰岛素抵抗和遗传对多囊卵巢综合征不孕症的贡献。项目I(莱格罗博士)将评估遗传标记D19S884是否识别出患多囊卵巢综合征风险增加的年轻女孩，以及该标记在识别患有早熟的女孩时的效用，这些女孩对二甲双胍有反应，以防止进展为多囊卵巢综合征。项目二(Nestler博士)提出了一项药物遗传学研究，以评估STK11基因中的SNP_rs8111669或项目III确定的其他候选基因中的SNPs对二甲双胍排卵反应的影响。相关的体外研究将确定SNP_rs9111699基因对培养的人卵泡膜细胞和肝细胞二甲双胍反应的影响。在识别PCOS易感基因(D19S884)方面发挥了关键作用的人类遗传学研究继续进行，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D19S884以外的PCOS候选基因，并将遗传分析从PCOS(质量性状)扩展到与PCOS相关的数量性状。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，并为SCCPRIR的成功运行提供样本、分析、招聘、广告和其他必要职能的集中处理。考虑到VCU最近招聘了一位新的医学院院长(Strauss博士)，并提供了新的资源来支持研究；致力于研究(特别是妇女健康)，建立了CTSA和NIH路线图；并在增加NIH资金方面取得了成功，因此这次申请续签SCCPRIR的时机特别及时。

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.