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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：量化与多囊卵巢综合征（PCOS），PCOS女性，PCOS女性的家庭成员以及对照组（无PCOS女性）相关的特定DNA多态性的患病率。 设计：前瞻性案例对照 研究计划：参与者包括18-39岁的妇女，并根据闭经/寡头疾病（10/年）诊断为PCOS，而无毛肌。 参与者将使用改良的Ferriman-Gallwey调查简要评估头发模式。 他们将具有血压，脉搏，高度和体重。 禁食10个小时后，受试者将有大约30 cc的血液用于激素水平和多态性研究。 血清样品将进行以下分析：葡萄糖，HBA1C，CBC，肝功能测试，脂质和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). 激素仅在生殖时代的女性上进行。 问卷，实验室结果和头发调查将用于确定一个人是否患有PCOS。 PCR的全血将在EDTA和冷冻中收集，并以-20摄氏度储存。候选基因将从已与PCOS，肥胖或糖尿病（例如β3肾上腺素能受体，TNF -Alpha，TNF -Alpha和胰岛素受体vntrtr）相关的（或将来鉴定）的候选基因中选择。 DNA将使用市售套件隔离。 特定感兴趣的基因将通过聚合酶链反应（PCR）分离并扩增。 PCR产品将与特定的限制酶孵育有关感兴趣的位点。 所得消化的DNA片段将在2.5％的琼脂糖凝胶上运行，用溴化乙锭染色，并在紫外线下进行分析。 PCOS组，家庭成员组和对照组将报告特定多态性的发生率。 临床相关性：PCOS（例如糖尿病）显示出暗示遗传联系的遗传。 基因将个体以不同程度的胰岛素抵抗，PCOS，2型糖尿病，甚至特定的最终器官损害的风险。 确定与PCOS相关的不同多态性和有价值的胰岛素耐药性，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，以表征并进一步定义PCOS中的特定子集。 未来的治疗方法将针对这些子集，以提高功效。