SNP Analysis of Endometriosis Candidate Genes

描述(申请人提供)：子宫内膜异位症是一种知之甚少的妇科疾病，定义为腹膜、卵巢和其他器官中存在子宫内膜组织。这种情况的特点是炎症、纤维化、粘连和巧克力囊肿，导致慢性盆腔疼痛、性交疼痛(性交困难)、痛经(痛经)和不孕不育。尽管子宫内膜异位症不会危及生命，但它继续使数百万女性丧失工作能力并影响她们的健康、生产力和生活方式，同时也给医生和研究人员带来了挑战。时至今日，子宫内膜异位症的病因仍然难以捉摸，尽管与环境、免疫和遗传因素有关。可用于治疗子宫内膜异位症的有限的治疗方法是不能治愈的。子宫内膜异位症的明确诊断需要手术，因为对这种疾病没有特异和敏感的诊断测试。在过去的几年里，我们的实验室一直在研究波多黎各子宫内膜异位症的分子和遗传学方面，具体目的是填补对这种疾病的一般知识的一个重要空白，并特别适用于拉美裔人口。我们实验室的初步研究表明，以前报道的与子宫内膜异位症有关的基因在我们的人群中并不成立。这些发现突显了在不同人群中进行关联研究的重要性，因为基因变异及其与疾病易感性的关系可能因种族背景而异。此外，我们还观察到，有和没有子宫内膜异位症家族的患者存在不同的遗传关联。最后，我们使用DNA微阵列、消减杂交和遗传连锁分析来确定可能代表子宫内膜异位症易感基因的候选基因和基因组区域。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有关。此外，我们假设家族性和散发性子宫内膜异位症患者的基因相关性不同。因此，本提案的主要目标是阐明波多黎各人群中子宫内膜异位症的遗传易感性所涉及的机制，并确定这些机制是否因家族史状况而不同。识别这些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，并最终开发治疗这种丧失能力的疾病是至关重要的。由于子宫内膜异位症与不孕症、妊娠丢失和异位妊娠之间的重要联系，这些研究发现的信息将极大地影响生殖科学领域，这是《人物2010》报告中讨论的一个目标问题。

DESCRIPTION (provided by applicant): Endometriosis is a poorly understood gynecologic condition defined as the presence of endometrial tissue in the peritoneum, ovaries, and other organs. This condition is characterized by inflammation, fibrosis, adhesions, and chocolate cysts, which result in chronic pelvic pain, pain during intercourse (dyspareunia), painful periods (dysmenorrhea), and infertility. Although not life-threatening, 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. Still today, the cause of endometriosis remains elusive, although environmental, immunological and genetic factors have been implicated. The limited treatments available for endometriosis are not curative. A definitive diagnosis of endometriosis requires surgery, since there are no specific and sensitive diagnostic tests for this disease. For the past years, our laboratory has been studying the molecular and genetic aspects of endometriosis in Puerto Rico, with the specific 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 and 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 pregnancies, the information uncovered by these studies will greatly impact the field of reproductive science, a target issue addressed in the People 2010 report.