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.

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：量化与多囊卵巢综合征（PCOS）、糖尿病和肥胖相关的特定DNA多态性在PCOS女性、PCOS女性家庭成员和对照组（无PCOS女性）中的患病率。 设计：前瞻性病例对照研究 研究对象：参与者包括18-39岁的女性，根据闭经/月经过少（10/年）和无多毛症诊断为PCOS。 参与者将使用修改后的Ferriman-Gallwey调查完成对头发图案的简要评估。 他们将测量血压、脉搏、身高和体重。 空腹10小时后，受试者将抽取约30 cc血液用于激素水平和多态性研究。 将对血清样本进行以下分析：葡萄糖、HbA 1C、CBC、肝功能检查、脂质和TSH。 将冷冻并储存血清样本，用于以下检测（当资金可用时）：总睾酮和游离睾酮、孕酮、催乳素、硫酸二氢表雄烯二酮（DHEAS）、17-羟孕酮、LH、FSH、胰岛素、组织纤溶酶原激活物（t-PA）、纤溶酶原激活物抑制剂1型（派-1）。 激素将仅在育龄女性身上运行。 将使用问卷、实验室结果和头发调查来确定一个人是否患有多囊卵巢综合症。 用于PCR的全血将采集在EDTA中，冷冻并储存在-20 ℃下。 候选基因将从那些已经与PCOS、肥胖或糖尿病相关（或将来被鉴定）的基因中选择（例如β 3肾上腺素能受体、TNF-α和胰岛素受体基因VNTR）。 将使用市售试剂盒分离DNA。 将分离感兴趣的特定基因，并使用聚合酶链反应（PCR）进行扩增。 PCR产物将与目标位点的特异性限制性内切酶一起孵育。 将所得消化的DNA片段在2.5%琼脂糖凝胶上电泳，用溴化乙锭染色，并在紫外光下分析。 将报告PCOS组、家族成员组和对照组中特定多态性的发生率。 临床相关性：多囊卵巢综合征，像糖尿病，显示遗传暗示的遗传连锁。 基因使个体处于不同程度的胰岛素抵抗、PCOS、2型糖尿病甚至特定终末器官损伤的风险中。 确定与PCOS和胰岛素抵抗相关的不同多态性是有价值的，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和实验室特征相关，以表征和进一步定义PCOS中的特定亚群。 未来的治疗将针对这些亚群，以提高疗效。