Department of Medicine and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA.
Semin Nephrol. 2017 Nov;37(6):508-513. doi: 10.1016/j.semnephrol.2017.07.003.
APOL1 kidney risk variants lead to high rates of kidney disease in people of recent African ancestry. These risk variants are very common and confer a large increase in risk of kidney disease. This unusual combination of high frequency and large effect size occurs because the risk variants also appear to have beneficial properties. The risk variants show enhanced protective effects against certain pathogens, particularly the trypanosomes that cause African sleeping sickness. Here, we consider the origins and evolution of the primate-only APOL1 gene. Human genetics, mouse models, biochemistry, and comparative genomics suggest that APOL1 is an innate immunity gene and that the risk variants have the potential for heightened immunity that comes at the cost of toxicity to the kidneys. A better understanding of the evolution of APOL1 may help illuminate how APOL1 causes kidney disease in individuals who harbor the high-risk variants.
APOL1 肾脏风险变异导致具有近期非洲血统的人群中肾脏疾病的高发病率。这些风险变异非常常见，并大幅增加了肾脏疾病的风险。这种高频率和大效应量的不寻常组合是因为风险变异似乎也具有有益的特性。风险变异对某些病原体（特别是引起非洲昏睡病的锥虫）表现出增强的保护作用。在这里，我们考虑灵长类动物特有的 APOL1 基因的起源和进化。人类遗传学、小鼠模型、生物化学和比较基因组学表明，APOL1 是一种先天免疫基因，风险变异具有增强免疫力的潜力，但代价是对肾脏的毒性。更好地了解 APOL1 的进化可能有助于阐明携带高风险变异的个体中 APOL1 如何导致肾脏疾病。
