APOL1 风险变异与基于人群的队列研究中的血清白蛋白相关。
APOL1 Risk Variants Associated with Serum Albumin in a Population-Based Cohort Study.
机构信息
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA,
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
出版信息
Am J Nephrol. 2022;53(2-3):182-190. doi: 10.1159/000520997. Epub 2022 Jan 31.
INTRODUCTION
The association of apolipoprotein L1 (APOL1) nephropathy risk variants (APOL1), unique to African-ancestry (African-American [AA]) populations, with systemic inflammation, a contributor to chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is ill-defined. This study aimed to describe the role of inflammatory markers in the relationship between APOL1 and incident kidney outcomes using a prospective cohort study.
METHODS
APOL1 high-risk status under a recessive genetic model was studied in 10,605 AA adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke study. The primary variables of interest were inflammatory markers: C-reactive protein (mg/dL), white blood cell count (cells/mm3), and serum albumin (sALB) (mg/dL). High inflammation status was defined if at least one of these inflammatory markers exceeded clinical threshold. The association between APOL1 and biomarkers were assessed using regression models adjusting for age, sex, ancestry, hypertension, lipid medications, albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR). Models were stratified by diabetes status. We identified incident ESKD using USRDS linkage, and we defined incident CKD as an eGFR <60 mL/min/1.73 m2 and ≥25% decline in the eGFR and normal baseline eGFR and tested for mediation of APOL1 and outcomes by biomarkers using the causal inference approach.
RESULTS
Among 7,151 participants with data available on all inflammation markers, 4,479 participants had ≥1 marker meeting the clinical threshold. APOL1 high-risk status was associated with lower adjusted odds of reduced sALB {odds ratio (OR) (95% confidence interval [CI]): 0.59 [0.36, 0.96])}, and this association was significant in people with diabetes (OR [95% CI]: 0.40 [0.18, 0.89]) but not in those without diabetes. There was no association of APOL1 high-risk status with other markers or high inflammation status. APOL1 was independently associated with ESKD (OR [95% CI] = 1.78 [1.28, 2.48]) and CKD (OR [95% CI] = 1.38 [1.00, 1.91]). On mediation analysis, the direct effect between APOL1 and ESKD strengthened after accounting for sALB, but the estimated mediated effect was not statistically significant (OR [95% CI]: 0.98 [0.92, 1.05], p = 0.58).
CONCLUSION
APOL1 high-risk variants were associated with sALB. However, sALB did not statistically mediate the association between APOL1 and incident ESKD.
介绍
载脂蛋白 L1（APOL1）肾病风险变异（APOL1）与全身炎症有关，这是一种独特的非洲裔（非裔美国人[AA]）人群的特征，也是慢性肾脏病（CKD）和终末期肾病（ESKD）的一个促成因素，但目前对此了解甚少。本研究旨在通过前瞻性队列研究，描述炎症标志物在 APOL1 与肾脏事件发生之间的关系中的作用。
方法
在 Reasons for Geographic and Racial Differences in Stroke 研究中，研究了 10605 名年龄≥45 岁的 AA 成年人中隐性遗传模型下的 APOL1 高危状态。主要的研究变量是炎症标志物：C 反应蛋白（mg/dL）、白细胞计数（细胞/mm3）和血清白蛋白（sALB）（mg/dL）。如果至少有一种炎症标志物超过临床阈值，则定义为高炎症状态。使用回归模型调整年龄、性别、祖源、高血压、降脂药物、白蛋白/肌酐比值和估计肾小球滤过率（eGFR），评估 APOL1 与生物标志物之间的关系。根据糖尿病状态对模型进行分层。我们通过 USRDS 链接识别新发 ESKD，并将新发 CKD 定义为 eGFR<60 mL/min/1.73 m2 且 eGFR 下降≥25%且基线 eGFR 正常，并使用因果推理方法测试生物标志物对 APOL1 和结局的中介作用。
结果
在 7151 名可提供所有炎症标志物数据的参与者中，有 4479 名参与者有≥1 种标志物符合临床阈值。APOL1 高危状态与较低的调整后 sALB 减少 odds 相关{比值比（OR）（95%置信区间[CI]）：0.59 [0.36, 0.96]}，并且这种关联在有糖尿病的参与者中具有统计学意义（OR [95% CI]：0.40 [0.18, 0.89]），但在没有糖尿病的参与者中没有统计学意义。APOL1 高危状态与其他标志物或高炎症状态均无关联。APOL1 与 ESKD（OR [95% CI] = 1.78 [1.28, 2.48]）和 CKD（OR [95% CI] = 1.38 [1.00, 1.91]）独立相关。在中介分析中，在考虑 sALB 后，APOL1 与 ESKD 之间的直接作用增强，但估计的中介作用没有统计学意义（OR [95% CI]：0.98 [0.92, 1.05]，p = 0.58）。
结论
APOL1 高危变异与 sALB 有关。然而，sALB 并没有在统计学上调节 APOL1 与新发 ESKD 之间的关联。
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