Racial Disparity for miRNAs in Uterine Leiomyomas

子宫肌瘤中 miRNA 的种族差异

基本信息

批准号：
7835776
负责人：
Jian-Jun Wei
金额：
$ 7.71万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-08 至 2011-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): It is well recognized that African American women have a higher rate, larger size and worse morbidity of uterine leiomyomata (ULM) than white women. Identification of the genetic variants and differences in gene expression in ULM of different races will greatly benefit our understanding of the molecular basis of disease risk. MicroRNAs are a group of small non-coding RNAs that are associated with tumorigenesis in many benign and malignant tumors. In our previous pilot study, we found some microRNAs were significantly differentially expressed in ULM between African American and white women. To determine whether the differentially expressed microRNAs in ULM of different races can be used as markers for risk evaluation in this study, we intend to validate our findings of miRNA expression between racial groups by examining a new large cohort ULM population of African American and white women. Specifically, we would like to know whether the racial differences in miRNA expression are evident in the disease related myometrium or only in ULM. Since several racially related miRNAs are aberrantly expressed in many other solid tumors, we propose that these highly dysregulated microRNAs in ULM of African American women are important contributors to ULM morbidity, due to their downregulation of some major target genes. Their functional roles in relation to leiomyoma growth will be investigated. The study can be accomplished by examining whether the significantly dysregulated microRNAs in ULM of African American women (African American related microRNAs) can regulate major target genes that are significantly dysregulated in ULMs. Accomplishment of the study will allow us to identify the microRNAs and their target genes in ULM as important molecular markers. Future studies will focus on: 1) whether there are potential functional polymorphisms due to the differential expression of the racially related microRNAs (in vitro functional analysis); 2) whether the genetic variants along these racially related microRNAs affect ULM susceptibility (case matched association study by SNP); and 3) whether the racially related microRNAs affect the expression of their target genes in ULM (chip based and case matched comparison of miRNAs and functional gene expression). The long term goal is to find molecular markers for early detections, prediction and prevention. PUBLIC HEALTH RELEVANCE: African American women have a higher rate, larger size and worse morbidity of uterine leiomyomata than white women. Identification of the genetic variants and differences in gene expression in ULM of different races will greatly benefit our understanding of the molecular basis of disease risk. In this study, we intend to identify the molecular differences in uterine leiomyomas between African American and white women.

描述（由申请人提供）：众所周知，非洲裔美国妇女比白人妇女更高，子宫平滑肌疗法（ULM）的发病率更高，而且发病率更高。鉴定遗传变异和不同种族ULM中基因表达的差异将极大地有助于我们对疾病风险分子基础的理解。 microRNA是一组与许多良性和恶性肿瘤中肿瘤发生有关的小型非编码RNA。在我们以前的试点研究中，我们发现在非裔美国人和白人妇女之间，在ULM中，一些microRNA在ULM中得到了显着差异。为了确定在本研究中，是否可以将不同种族的ULM中差异表达的microRNA用作风险评估的标志物，我们打算通过研究非裔美国人和白人女性的新大型ULM ULM人口来验证种族群体之间的miRNA表达结果。具体而言，我们想知道miRNA表达的种族差异在与肌矩阵相关的疾病中还是仅在ULM中显而易见。由于在许多其他实体瘤中都异常表达了几种与种族相关的miRNA，因此我们认为，由于某些主要靶基因的下调，非裔美国妇女ULM中这些高度失调的microRNA是ULM发病率的重要促进者。将研究它们与平滑肌瘤生长有关的功能作用。这项研究可以通过检查非裔美国妇女（非裔美国人相关microRNA）中明显失调的microRNA是否可以调节ULM中明显失调的主要靶基因。这项研究的完成将使我们能够在ULM中识别MicroRNA及其靶基因作为重要的分子标记。未来的研究将重点介绍：1）由于种族相关的microRNA的差异表达，是否存在潜在的功能多态性（体外功能分析）； 2）这些与种族相关的microRNA沿途的遗传变异是否会影响ULM的敏感性（SNP案例匹配的关联研究）； 3）种族相关的microRNA是否会影响其在ULM中其靶基因的表达（基于芯片的miRNA和功能基因表达的比较）。长期目标是找到早期检测，预测和预防的分子标记。公共卫生相关性：非洲裔美国妇女比白人妇女更高，大小更大，并且子宫平滑肌的发病率更高。鉴定遗传变异和不同种族ULM中基因表达的差异将极大地有助于我们对疾病风险分子基础的理解。在这项研究中，我们打算确定非洲裔美国妇女和白人妇女之间子宫平滑肌瘤的分子差异。