非洲裔儿童和青年的 APOL1 基因风险与肾脏疾病。
Genetic risk of APOL1 and kidney disease in children and young adults of African ancestry.
机构信息
Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.
Department of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
出版信息
Curr Opin Pediatr. 2018 Apr;30(2):252-259. doi: 10.1097/MOP.0000000000000603.
PURPOSE OF REVIEW
Understanding the genetic risk of APOL1 in children and young adults is important given the lifetime risk of hypertension and kidney disease among children of African descent. We review recent epidemiologic and biologic findings on the effects of APOL1 and kidney disease.
RECENT FINDINGS
APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially among those with glomerular causes of kidney disease, and those affected by sickle cell disease or HIV. There are conflicting data on the APOL1 association with cardiovascular disease in children and young adults. APOL1 functions as part of the innate immune system. Podocyte expression of APOL1 likely contributes to the development of kidney disease. In cell culture and model organisms, APOL1 expression disrupts autophagic and ion flux, leads to defects in mitochondrial respiration and induces cell death.
SUMMARY
APOL1 explains almost 70% of the excess risk of kidney disease in those of African descent, and is common in children with glomerular disease. An evolving understanding of the pathogenesis of APOL1-mediated kidney damage may aid in personalized medicine approaches to APOL1 attributable kidney disease.
目的综述：了解非洲裔儿童和年轻人的 APOL1 遗传风险很重要，因为他们终生患高血压和肾脏疾病的风险很高。我们回顾了 APOL1 和肾脏疾病的最新流行病学和生物学研究结果。
最新发现：APOL1 与儿童和年轻人的高血压、蛋白尿以及肾功能下降更快和进展为终末期肾病有关，尤其是在肾小球疾病患者以及患有镰状细胞病或 HIV 的患者中。APOL1 与儿童和年轻人的心血管疾病之间的关联存在矛盾的数据。APOL1 作为先天免疫系统的一部分发挥作用。足细胞表达的 APOL1 可能导致肾脏疾病的发生。在细胞培养和模式生物中，APOL1 的表达会破坏自噬和离子流，导致线粒体呼吸缺陷并诱导细胞死亡。
总结：APOL1 解释了非洲裔人群中肾脏疾病风险增加的近 70%，并且在患有肾小球疾病的儿童中很常见。对 APOL1 介导的肾脏损伤发病机制的不断深入了解可能有助于针对 APOL1 相关肾脏疾病的个体化医疗方法。
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