Community-Based Evaluation of APOL1 Genetic Testing in African Americans

 描述（由申请人提供）：终末期肾病（ESRD）或肾衰竭影响美国超过50万人，并且不成比例地影响种族和少数民族人群。与白人相比，非洲裔美国人患ESRD的可能性高2-4倍，占ESRD人口的32%，而仅占美国人口的13%。载脂蛋白L1（APOL 1）基因的两个独立变体G1和G2与非洲裔美国人发生非糖尿病ESRD的风险增加7至10倍相关。此外，遗传两种风险变体（G1/G1，G2/G2或G1/G2）的人也更有可能在更年轻的时候发展为ESRD，并且接受来自具有两种风险变体的已故个体的供体肾脏的个体经历较短的肾脏移植存活。目前尚不清楚是否每个具有高风险基因型的人都会发展为ESRD; APOL 1相关风险的确切损伤机制或其与环境暴露的关系;或者患有共病的人是否更有可能发展为ESRD。为了解决这些不确定性，需要进行包括评估APOL 1状态在内的研究。APOL 1检测也可以提供给非裔美国人患者，以指导慢性肾脏疾病（CKD）的管理或作为旨在减少肾脏疾病的预防工作的一部分，并已被提议作为肾移植方案的一部分。然而，由于APOL 1变异体的临床意义存在不确定性，检测也可能产生困惑、焦虑或耻辱。需要多种形式的证据，包括社区成员的意见，以支持负责任的方法，在研究和临床护理中提供有关APOL 1状态的信息。研究目的：确定非洲裔美国人社区对向研究参与者返回有关APOL 1风险变异的信息以及在临床护理和肾移植计划中检测APOL 1风险变异的风险和益处的看法，并促进将这些观点纳入政策讨论。为此，该提案的具体目标是： 目标1：与研究人员，临床医生，社区领导人和非裔美国人进行关键线人访谈，以确定他们对向研究参与者提供APOL 1结果以及在临床护理和肾移植计划中使用APOL 1测试的看法。目标二：开展三个以社区为基础的审议小组，以确定社区的偏好和优先事项，以负责任的方式向研究参与者提供APOL 1结果，并在临床护理和肾移植计划中利用APOL 1检测。目标3：召开国家利益相关者会议，审查APOL 1相关肾脏疾病的当前科学，审查审议小组的结果，并为政策制定者制定指南。该项目的成功完成将为研究人员、临床医生和政策制定者提供基于社区的指导，指导他们如何将APOL 1结果返回研究和在临床护理中使用APOL 1检测。PHS 398/2590（2004年9月修订，2006年4月重新发布）

 DESCRIPTION (provided by applicant): Endstage renal disease (ESRD) or kidney failure affects over 500,000 persons in the United States and disproportionately affects racial and ethnic minority populations. Compared to whites, African Americans are 2-4 times more likely to develop ESRD, and represent 32% of the ESRD population, while only representing 13% of the US population. Two independent variants of the Apolipoprotein L1 (APOL1) gene, G1 and G2, have been associated with a 7 to 10-fold greater risk of developing non-diabetic ESRD in African Americans. Furthermore, people who inherit two risk variants (G1/G1, G2/G2 or G1/G2) are also more likely to develop ESRD at a younger age, and Individuals receiving donor kidneys from deceased individuals with two risk variants experience shorter kidney transplant survival. It is not known whether everyone with high- risk genotypes will develop ESRD; the exact mechanism of injury for APOL1-related risk or its relation to environmental exposures; or whether those with co-morbid conditions are more likely to develop ESRD. To address these uncertainties, research that includes assessment of APOL1 status will be needed. APOL1 testing may also be offered to African American patients to guide management of chronic kidney disease (CKD) or as part of prevention efforts aimed at reducing kidney disease, and has been proposed as part of kidney transplant protocols. Yet because of uncertainties regarding the clinical implications of APOL1 variants, testing could also generate confusion, anxiety or stigma. Multiple forms of evidence, including the views of community members, are needed to support responsible approaches to providing information about APOL1 status in research and clinical care. Research Goal: To determine African-American community views concerning the risks and benefits of returning information about APOL1 risk variants to research participants and testing for APOL1 risk variants in clinical care and renal transplant programs, and to promote inclusion of those views in policy discussions. To that end, the specific aims of the proposal are: Aim 1: Conduct key informant interviews with researchers, clinicians, community leaders, and African Americans with and without kidney disease, to determine their views about providing APOL1 results to research participants and utilizing APOL1 testing in clinical care, and renal transplant programs. Aim 2: Conduct three community-based deliberative groups to identify community preferences and priorities for responsible approaches to providing APOL1 results to research participants and utilizing APOL1 testing in clinical care and renal transplant programs. Aim 3: Convene a national meeting of stakeholders to review the current science of APOL1-related kidney disease, review findings of the deliberative groups, and develop guidance for policy-makers. The successful completion of this project will provide community-based guidance to researchers, clinicians and policy makers regarding the return of APOL1 results in research and the use of APOL1 testing in clinical care. PHS 398/2590 (Rev. 09/04, Reissued 4/2006)