Sarcoidosis in U.S. Black Women: Genetic and Non-genetic Risk Factors

描述(由申请人提供)： 这个K01应用程序的目的是支持Yvette Cozier博士进行一段时间的教学培训和指导性研究，以研究黑人女性结节病的遗传和非遗传病因。科齐尔博士的长期目标是缩小健康差距。作为波士顿大学公共卫生学院的助理教授和斯隆流行病学中心从事黑人女性健康研究(BWHS)的流行病学家，她将利用这两个群体的优势：统计遗传学方面的专业知识，美国黑人女性大型后续研究的丰富数据库，研究黑人女性疾病的专业知识，以及结节病的临床知识。她的导师在所有这些领域都有专业知识。 科齐尔博士将对黑人女性结节病的特定遗传和非遗传潜在风险因素进行研究。结节病是一种慢性肉芽肿性系统性疾病。就发病率而言，黑人女性在美国承担着结节病的最大负担，而且她们比任何其他群体更有可能被诊断为年轻，经历进展性疾病，以及死亡。关于这种疾病的原因，人们几乎没有建立起什么。这项拟议的研究将在BWHS内进行，这是一项对5.9万名美国黑人女性的前瞻性跟踪调查。从1995年开始，BWHS每两年收集一次关于包括结节病在内的疾病诊断和潜在风险因素的自我报告数据。此外，BWHS还收集了参与者的脸颊细胞样本，从中提取DNA进行遗传分析。只有通过病历/医生清单或补充问卷提供的信息核实的自行报告的结节病病例才会包括在内。这项验证研究已经与波士顿医学中心结节病诊所的肺科医生合作进行，已被证明是可行的。由于对免疫功能的影响，与压力相关的因素--经常经历种族主义和较低的社区社会经济地位--将被评估为结节病的危险因素。由于结节病倾向于影响女性，因此也将重点关注雌激素的暴露。内源性和外源性雌激素暴露的标志物，如月经初潮年龄和口服避孕药的使用，将分别与结节病的风险进行评估。我们还将评估与性激素代谢有关的基因的等位基因，包括那些与性激素合成有关的基因(CYP17、CYP19)，以及与雌激素的代谢和解毒有关的基因(COMT、CYP1B1、CYP1A1、ESR1)，与结节病的风险有关。 这些项目的最终目标是提高对结节病病因的理解，并发展Cozier博士独立扩展这项研究的能力。(摘要结束)

DESCRIPTION (provided by applicant): The purpose of this K01 application is to support a period of didactic training and mentored research for Dr. Yvette Cozier to study the genetic, as well as non-genetic, etiology of sarcoidosis in black women. Dr. Cozier's long term goal is to reduce health disparities. As an Assistant Professor at the Boston University School of Public Health, and an Epidemiologist at the Slone Epidemiology Center working on Black Women's Health Study (BWHS), she will draw on the strengths of both groups: expertise in statistical genetics, a rich database from a large follow-up study of U.S. black women, the expertise to study illness in black women, and clinical knowledge in sarcoidosis. Her mentors have expertise in all of these areas. Dr. Cozier will conduct a study of selected genetic and non-genetic potential risk factors for sarcoidosis, a chronic, granulomatous, systemic disorder, in black women. Black women bear the largest burden of sarcoidosis in the U.S in terms of incidence, and they are more likely than any other group to be younger at diagnosis, experience progressive disease, and die. Little is established about causes of the disease. The proposed study will be conducted within the BWHS, a prospective follow-up of 59,000 U.S. black women. Begun in 1995, the BWHS has collected self-reported data every two years on diagnoses of illness, including sarcoidosis, and on potential risk factors. In addition, the BWHS has collected cheek cell samples from participants, from which DMAis extracted for genetic analyses. Only self-reported cases of sarcoidosis validated by medical record/physician checklist or information from supplementary questionnaires will be included. The validation study, already in progress in collaboration with pulmonologists at the Sarcoidosis Clinic at Boston Medical Center, has been shown to be feasible. Because of effects on immune function, stress-related factors - - frequent experiences of racism and lower neighborhood socioeconomic status - - will be assessed as risk factors for sarcoidosis. Because of the propensity of sarcoidosis to affect women, there will also be a focus on estrogen exposure. Markers of endogenous and exogenous estrogen exposure, such as age at menarche and oral contraceptive use, respectively, will be assessed in relation to the risk of sarcoidosis. We will also assess alleles of genes involved in sex hormone metabolism, including those involved in the synthesis of sex steroids (CYP17, CYP19), and the metabolism and detoxification of estrogen (COMT, CYP1B1, CYP1A1, ESR1), in relation to sarcoidosis risk. The ultimate goal of these projects is to improve understanding of the etiology of sarcoidosis, and to develop Dr. Cozier's capability to independently extend this research. (End of Abstract)