THE GENETIC INHERITANCE OF POLYCYSTIC OVARY SYNDROME

多囊卵巢综合症的基因遗传

• 批准号: 7627547
• 负责人: ROBERT G BRZYSKI
• 金额: $ 0.5万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627547
• 关键词: Age; Alteplase; Amenorrhea; Blood; Blood Pressure; Candidate Disease Gene; Computer Retrieval of Information on Scientific Projects Database; Control Groups; DNA; Diabetes Mellitus; Diagnosis; Disease Progression; Edetic Acid; Ethnic Origin; Family member; Fasting; Female; Follicle Stimulating Hormone; Freezing; Funding; Future; Gel; Genes; Genetic; Genetic Polymorphism; Glucose; Glycosylated hemoglobin A; Grant; Hair; Height; Hirsutism; Homidium Bromide; Hormonal; Hormones; Hour; Hydroxyprogesterone; Incubated; Individual; Inorganic Sulfates; Institution; Insulin; Insulin Receptor; Insulin Resistance; Laboratories; Lipids; Liver Function Tests; Minisatellite Repeats; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oligomenorrhea; Organ; Participant; Patients; Pattern; Persons; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Polymerase Chain Reaction; Prevalence; Progesterone; Prolactin; Pulse Pressure; Questionnaires; Rate; Receptor Gene; Receptors, Adrenergic, beta-3; Reporting; Research; Research Personnel; Resources; Risk; Running; Sampling; Sepharose; Serum; Site; Source; Staining method; Stains; Surveys; Testosterone; Tumor Necrosis Factor-alpha; Ultraviolet Rays; United States National Institutes of Health; Unspecified or Sulfate Ion Sulfates; Weights and Measures; Whole Blood; Woman; aged; base; case control; clinically relevant; design; genetic linkage; human TNF protein; improved; interest; prospective; reproductive; response; restriction enzyme

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. OBJECTIVE: Quantify the prevalence of specific DNA polymorphisms associated with polycystic ovary syndrome (PCOS), diabetes, and obesity in women with PCOS, family members of women with PCOS, and controls (women without PCOS). DESIGN: Prospective case-control RESEARCH PLAN: Participants include women aged 18-39 with a diagnosis of PCOS based upon amenorrhea/oligomenorrhea (10/year) and no hirsutism. Participants will complete a brief assessment of hair patterns using the modified Ferriman-Gallwey survey. They will have blood pressure, pulse, height, and weight measured. After fasting for 10 hours, subjects will have approximately 30 cc of blood drawn for hormonal levels and polymorphism studies. Serum samples will be analyzed for the following: glucose, HbA1C, CBC, liver function tests, lipids, and TSH. Serum samples will be frozen and stored for the following (when funding becomes available): total and free testosterone, progesterone, prolactin, dihydoepiandrostendione sulfate (DHEAS), 17-hydroxyprogesterone, LH, FSH, insulin, tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1). Hormones will be run on reproductive-aged females only. Questionnaire, lab results, and hair survey will be used to determine if a person has PCOS. Whole blood for PCR will be collected in EDTA and frozen and stored at -20 degrees C. Candidate genes will be chosen from those which have been associated (or are identified in the future) with PCOS, obesity, or diabetes (such as the Beta 3 adrenergic receptor, TNF-Alpha, and insulin receptor gene VNTR). DNA will be isolated using a commercially available kit. Specific genes of interest will be isolated and amplified with polymerase chain reaction (PCR). PCR products will be incubated with specific restriction enzymes for sites of interest. Resulting digested DNA fragments will be run on a 2.5% agarose gel, stained with ethidium bromide, and analyzed under ultraviolet light. Occurrence rates of specific polymorphisms will be reported in the PCOS groups, family member group, and control group. CLINICAL RELEVANCE: PCOS, like diabetes, displays an inheritance suggestive of a genetic linkage. Genes place individuals at varying degrees of risk for insulin resistance, PCOS, type 2 diabetes, and even specific end organ damage. Determining distinct polymorphisms associated with PCOS and insulin resistance in valuable because it may predict a patient's disease progression or response to treatment. Specific polymorphisms will be correlated with ethnicity, BMI, and laboratory profiles to characterized and further define specific subsets within PCOS. Future treatments will be targeted to these subsets to improve efficacy.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：量化 PCOS 女性、PCOS 女性家庭成员和对照组（无 PCOS 的女性）中与多囊卵巢综合征 (PCOS)、糖尿病和肥胖相关的特定 DNA 多态性的患病率。 设计：前瞻性病例对照 研究计划：参与者包括 18-39 岁、因闭经/月经稀发（10 次/年）且无多毛症而诊断为 PCOS 的女性。 参与者将使用修改后的费里曼-加威调查完成对头发图案的简短评估。 他们将测量血压、脉搏、身高和体重。 禁食 10 小时后，受试者将抽取约 30 cc 的血液用于激素水平和多态性研究。 将分析血清样本的以下项目：葡萄糖、HbA1C、CBC、肝功能测试、血脂和 TSH。 血清样本将被冷冻并储存用于以下项目（当资金到位时）：总睾酮和游离睾酮、黄体酮、催乳素、硫酸二氢表雄烯二酮 (DHEAS)、17-羟基孕酮、LH、FSH、胰岛素、组织纤溶酶原激活剂 (t-PA) ，纤溶酶原激活剂抑制剂 1 型 (PAI-1)。 激素仅适用于育龄女性。 问卷、实验室结果和头发调查将用于确定一个人是否患有多囊卵巢综合症。 用于 PCR 的全血将被收集在 EDTA 中并冷冻并储存在 -20 摄氏度。候选基因将从与 PCOS、肥胖或糖尿病相关（或将来确定）的基因中选择（例如 Beta 基因）。 3 肾上腺素能受体、TNF-α 和胰岛素受体基因 VNTR）。 DNA 将使用市售试剂盒进行分离。 将通过聚合酶链式反应 (PCR) 分离和扩增特定的感兴趣基因。 PCR 产物将与感兴趣位点的特定限制性酶一起孵育。 所得消化后的 DNA 片段将在 2.5% 琼脂糖凝胶上进行电泳，用溴化乙锭染色，并在紫外光下进行分析。 将报告 PCOS 组、家庭成员组和对照组中特定多态性的发生率。 临床相关性：多囊卵巢综合症与糖尿病一样，表现出暗示遗传联系的遗传性。 基因使个体面临不同程度的胰岛素抵抗、多囊卵巢综合症、2型糖尿病，甚至特定终末器官损伤的风险。 确定与 PCOS 和胰岛素抵抗相关的不同多态性很有价值，因为它可以预测患者的疾病进展或对治疗的反应。 特定的多态性将与种族、BMI 和实验室概况相关联，以表征并进一步定义 PCOS 内的特定子集。 未来的治疗将针对这些子集以提高疗效。