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

非洲特有变异体与慢性肾脏疾病的先导研究 这项先导性研究的总体目标是提供更多的数据来支持更大的R01应用，该应用为非洲特有的风险等位基因(APOL1和镰状细胞特性[SCT]rs334变体)以及APOL1和SCT的新型遗传和环境修饰物在非裔美国人慢性肾脏疾病和终末期肾脏疾病风险方面的作用定义了新的方向。我们的主要目标是更好地了解临床上观察到的携带这些高危基因的非裔美国人肾脏疾病风险和进展的变化。慢性肾脏疾病是一种破坏性的疾病，与巨大的心血管疾病负担和社会经济成本有关。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5-29倍，但在人群研究中，仅使慢性肾脏疾病的风险增加2倍。SCT在进展为终末期肾脏疾病中的作用尚不清楚。我们的研究假设是，到目前为止，尚未确定的遗传和环境因素解释了具有这些风险等位基因的个体中慢性肾脏疾病的不同临床外显性。利用美国最大的非裔美国人人口纵向数据集的现有但尚未开发的生物库资源，我们将对来自妇女健康倡议的3,826名非裔美国女性进行基线血清肌酐测量，从而对非裔美国人与APOL1和SCT相关的慢性肾脏疾病的风险和进展进行前所未有的检查。

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.