SNP Analysis of Endometriosis Candidate Genes

子宫内膜异位症候选基因的SNP分析

• 批准号: 7102207
• 负责人: IDHALIZ FLORES
• 金额: $ 32.14万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-24 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102207
• 关键词: Puerto Rican; clinical research; disease /disorder classification; endometriosis; family genetics; female; gene expression profiling; gene mutation; genetic susceptibility; human genetic material tag; human subject; linkage mapping; microarray technology; molecular genetics; single nucleotide polymorphism; women' s health

DESCRIPTION (provided by applicant): Endometriosis is a poorly understood gynecologic condition defined as the presence of endometrial tissue at ectopic sites. This condition is characterized by severe pelvic pain, dyspareunia, dysmenorrhea, and infertility. Endometriosis continues to incapacitate and affect the well being, productivity, and lifestyle of millions of women, whilst imposing a challenge to medical doctors and researchers alike. The cause of endometriosis remains elusive, although environmental, immunological and genetic factors have been implicated. The limited treatments available are not curative, and definitive diagnosis requires surgery, since there are no specific diagnostic tests for this disease. We have been studying the molecular and genetic aspects of endometriosis in Puerto Rico, with the purpose of filling an important gap in the knowledge of this disease in general, and also as its applies to the Hispanic population in particular. Preliminary studies in our laboratory have shown that previously reported genetic associations to endometriosis do not hold true in our population. These findings highlight the importance of carrying out association studies in different populations, since genetic variations and their involvement in disease susceptibility are likely to vary across ethnic backgrounds. Also, we have observed that genetic associations differ in patients with and without a family of endometriosis. Finally, we have used DNA microarrays, subtractive hybridization and genetic linkage analysis to identify candidate genes/genomic regions which potentially represent susceptibility loci for endometriosis. We hypothesize that genetic variations in candidate genes are associated with susceptibility to endometriosis. Also, we hypothesize that genetic associations differ in patients with familial versus sporadic endometriosis. The main goal of the present proposal, therefore, is to elucidate the mechanisms involved in the genetic susceptibility to endometriosis in a Puerto Rican population, and to determine if those mechanisms vary according to family history status. Identification of such variations is of critical importance to better understand the etiology of endometriosis, to design specific non-invasive diagnostic tests and, ultimately, to develop a cure for this incapacitating condition. Due to important links between endometriosis and infertility, pregnancy loss and ectopic pregnancy, the information uncovered by these studies will greatly impact the field of reproductive science, a target issue addressed in the Healthy People 2010 report (9-12).

描述（由申请人提供）：子宫内膜异位症是一种人们知之甚少的妇科疾病，其定义为异位部位存在子宫内膜组织。这种疾病的特点是严重的盆腔疼痛、性交痛、痛经和不孕。子宫内膜异位症继续使数百万女性丧失能力，影响她们的健康、生产力和生活方式，同时给医生和研究人员带来挑战。尽管环境、免疫和遗传因素与子宫内膜异位症的病因有关，但其病因仍然难以捉摸。可用的有限治疗方法无法治愈，并且由于没有针对这种疾病的具体诊断测试，因此明确的诊断需要手术。我们一直在波多黎各研究子宫内膜异位症的分子和遗传方面，目的是填补对该疾病的一般知识的重要空白，以及它特别适用于西班牙裔人群的知识。我们实验室的初步研究表明，先前报道的与子宫内膜异位症的遗传关联在我们的人群中并不成立。这些发现强调了在不同人群中进行关联研究的重要性，因为遗传变异及其对疾病易感性的影响可能因种族背景而异。此外，我们还观察到，有子宫内膜异位症家族的患者和没有子宫内膜异位症家族的患者之间的遗传关联有所不同。最后，我们使用DNA微阵列、消减杂交和遗传连锁分析来鉴定可能代表子宫内膜异位症易感位点的候选基因/基因组区域。我们假设候选基因的遗传变异与子宫内膜异位症的易感性相关。此外，我们假设家族性子宫内膜异位症患者与散发性子宫内膜异位症患者的遗传关联不同。因此，本提案的主要目标是阐明波多黎各人群子宫内膜异位症遗传易感性的机制，并确定这些机制是否根据家族史状况而变化。识别此类变异对于更好地了解子宫内膜异位症的病因、设计特定的非侵入性诊断测试以及最终开发针对这种致残性疾病的治疗方法至关重要。由于子宫内膜异位症与不孕症、流产和宫外孕之间存在重要联系，这些研究发现的信息将极大地影响生殖科学领域，这是《2010 年健康人》报告 (9-12) 中讨论的一个目标问题。