Genetic variants in the APOL1 gene, found only in individuals of recent African ancestry, greatly increase risk of multiple types of kidney disease. These APOL1 kidney risk alleles are a rare example of genetic variants that are common but also have a powerful effect on disease susceptibility. These alleles rose to high frequency in sub-Saharan Africa because they conferred protection against pathogenic trypanosomes that cause African sleeping sickness. We consider the genetic evidence supporting the association between APOL1 and kidney disease across the range of clinical phenotypes in the APOL1 nephropathy spectrum. We then explore the origins of the APOL1 risk variants and evolutionary struggle between humans and trypanosomes at both the molecular and population genetic level. Finally, we survey the rapidly growing literature investigating APOL1 biology as elucidated from experiments in cell-based systems, cell-free systems, mouse and lower organism models of disease, and through illuminating natural experiments in humans.

中文翻译：

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APOL1和肾脏疾病：从遗传学到生物学。

仅在最近的非洲血统的个体中发现的APOL1基因的遗传变异大大增加了多种类型肾脏疾病的风险。这些APOL1肾脏风险等位基因是常见的遗传变异的罕见例子，但对疾病的易感性也具有强大的作用。这些等位基因在撒哈拉以南非洲地区频率较高，因为它们赋予了针对引起非洲昏睡病的病原性锥虫的保护。我们认为遗传证据支持APOL1肾病谱中临床表型范围内APOL1与肾脏疾病之间的关联。然后，我们在分子和种群遗传水平上探索APOL1风险变异的起源以及人类与锥虫之间的进化斗争。最后，