Introduction: The G1 and G2 variants in the APOL1 gene convey high risk for the progression of chronic kidney disease in African Americans. The G3 variant in APOL1 is more common in patients of European ancestry (EA); outcomes associated with this variant have not been explored previously in EA patients receiving dialysis. Methods: DNA was collected from approximately half of the patients enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial and genotyped for the G3 variants. We utilized an additive genetic model to test associations of G3 with the EVOLVE adjudicated endpoints of all-cause mortality, cardiovascular mortality, sudden cardiac death (SCD), and heart failure. EA and African ancestry samples were analyzed separately. Validation was done in the Vanderbilt BioVU using ICD codes for cardiovascular events that parallel the adjudicated endpoints in EVOLVE. Results: In EVOLVE, G3 in EA patients was associated with the adjudicated endpoints of cardiovascular mortality and SCD. In a validation cohort from the Vanderbilt BioVU, cardiovascular events and cardiovascular mortality defined by ICD codes showed similar associations in EA participants who had been on dialysis for 2 to #x3c;5 years. Discussion/Conclusions: G3 in APOL1 variant was associated with cardiovascular events and cardiovascular mortality in the EA patients receiving dialysis. This suggests that variations in the APOL1 gene that differ in populations of different ancestry may contribute to cardiovascular disease.
Cardiorenal Med

中文翻译：

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APOL1 G3 变异与接受欧洲血统维持性血液透析的患者的心血管死亡率和心源性猝死相关

简介： APOL1基因中的 G1 和 G2 变异表明非裔美国人患慢性肾病的风险很高。APOL1中的 G3 变异在欧洲血统 (EA) 患者中更为常见；之前尚未在接受透析的 EA 患者中探索与该变异相关的结果。方法：从参加盐酸西那卡塞治疗降低心血管事件评估 (EVOLVE) 试验的大约一半患者中收集 DNA，并对 G3 变异进行基因分型。我们利用加性遗传模型来测试 G3 与 EVOLVE 判定的全因死亡率、心血管死亡率、心源性猝死 (SCD) 和心力衰竭终点的关联。EA 和非洲血统样本分别进行了分析。验证是在 Vanderbilt BioVU 中使用与 EVOLVE 中判定的终点平行的心血管事件 ICD 代码进行的。结果：在 EVOLVE 中，EA 患者的 G3 与心血管死亡率和 SCD 的判定终点相关。在 Vanderbilt BioVU 的验证队列中，由 ICD 代码定义的心血管事件和心血管死亡率在接受透析 2 至 #x3c;5 年的 EA 参与者中显示出类似的关联。讨论/结论： APOL1变异中的 G3与接受透析的 EA 患者的心血管事件和心血管死亡率相关。这表明不同血统人群中APOL1基因的变异可能会导致心血管疾病。
心肾医学