Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN; Vanderbilt Center for Kidney Disease, Nashville, TN.
Nephrology, Hospital and Specialty Medicine and Center for Innovation for Veteran-Centered and Value Driven Care, Veterans Affairs Puget Sound Health Care System, Seattle, WA; Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, WA.
Am J Kidney Dis. 2019 Dec;74(6):811-821. doi: 10.1053/j.ajkd.2019.06.006. Epub 2019 Oct 10.
African Americans have a 2- to 4-fold greater incidence of end-stage kidney disease (ESKD) than whites, which has long raised the possibility of a genetic cause for this disparity. Recent advances in genetic studies have shown a causal association of polymorphisms at the apolipoprotein L1 gene (APOL1) with the markedly increased risk for the nondiabetic component of the overall disparity in ESKD in African Americans. Although APOL1-associated kidney disease is thought to account for a substantial proportion of ESKD in African Americans, not all the increased risk for ESKD is accounted for, and a complete cataloging of disparities in genetic causes of ESKD eludes our current understanding of genetic-associated kidney disease. Genetic testing aids the screening, diagnosis, prognosis, and treatment of diseases with a genetic basis. Widespread use of genetic testing in clinical practice is limited by the small number of actionable genetic variants, limited health literacy of providers and patients, and underlying complex ethical, legal, and social issues. This perspective reviews racial and ethnic differences associated with genetic diseases and the development of ESKD in African Americans and discusses potential uncertainties associated with our current understanding of penetrance of genetically linked kidney disease and population-attributable risk percent.
非裔美国人终末期肾病（ESKD）的发病率比白人高 2 至 4 倍，这长期以来一直让人怀疑这种差异可能存在遗传原因。遗传研究的最新进展表明，载脂蛋白 L1 基因（APOL1）的多态性与非糖尿病患者中非裔美国人 ESKD 整体差异的风险显著增加之间存在因果关系。尽管 APOL1 相关的肾脏疾病被认为是导致非裔美国人 ESKD 的一个重要原因，但并非所有 ESKD 的风险增加都可以用它来解释，而且我们目前对遗传相关肾脏疾病的理解还无法完全解释 ESKD 遗传病因的差异。基因检测有助于对具有遗传基础的疾病进行筛查、诊断、预后和治疗。基因检测在临床实践中的广泛应用受到以下因素的限制：可采取行动的遗传变异数量有限、提供者和患者的健康素养有限，以及潜在的复杂伦理、法律和社会问题。本观点回顾了与遗传疾病和非裔美国人 ESKD 相关的种族和民族差异，并讨论了与我们目前对遗传相关肾脏疾病的外显率和人群归因风险百分比的理解相关的潜在不确定性。
