APOL1, sickle cell trait and chronic kidney disease in African Americans

非洲特异性变异与慢性肾脏病的初步研究 这项试点研究的首要目标是提供额外的数据，以支持更大的R01应用程序，该应用程序定义了非洲特异性风险等位基因（APOL1和镰状细胞性状[SCT] rs334变体）以及APOL1和SCT的新型遗传和环境修饰剂在非裔美国人慢性肾脏疾病和终末期肾脏疾病风险中的作用的新方向。我们的主要目标是更好地了解携带这些高风险基因型的非裔美国人临床观察到的不同肾脏疾病风险和进展。慢性肾脏疾病是一种与大量心血管疾病负担和社会经济成本相关的破坏性疾病。在病例对照研究中，APOL1风险等位基因使终末期肾病的风险增加5至29倍，但在人群研究中，慢性肾病的风险仅增加2倍。SCT在进展为终末期肾病中的作用尚不清楚。我们的研究假设是，尚未确定的遗传和环境因素解释了具有这些危险等位基因的个体中慢性肾脏疾病的可变临床发病率。利用现有的，但尚未开发的生物资源库的最大的人口为基础的纵向数据集的非洲裔美国人在美国，我们将对来自妇女健康倡议的3，826名非裔美国妇女进行基线血清肌酐测量，以前所未有地检查非裔美国人中与APOL 1和SCT相关的慢性肾脏疾病的风险和进展。

Pilot study of African-specific variants and chronic kidney disease The over-arching goal of this pilot study is to provide additional data to support a larger R01 application that defines new directions for the roles of African-specific risk alleles (APOL1 and the sickle cell trait [SCT] rs334 variant), and novel genetic and environmental modifiers of APOL1 and SCT, on risk of chronic kidney disease and end-stage renal disease in African Americans. Our main goal is to better understand the clinically observed varying kidney disease risk and progression in African Americans carrying these high risk genotypes. Chronic kidney disease is a devastating condition associated with substantial cardiovascular disease burden, and socio-economic cost. APOL1 risk alleles confer 5- to 29-fold increased risk to end-stage renal disease in case-control studies, but only a 2-fold risk to chronic kidney disease in population studies. The role of SCT in progression to end-stage renal disease remains unclear. Our research hypothesis is that as yet unidentified genetic and environmental factors explain the variable clinical penetrance of chronic kidney disease in individuals with these risk alleles. Leveraging the existing, but untapped biorepository resource of the largest population-based longitudinal data set of African Americans in the U.S., we will perform baseline serum creatinine measurements in 3,826 African American women from the Women’s Health Initiative, to allow an unprecedented examination of the risk and progression of chronic kidney disease associated with APOL1 and SCT in African Americans.