JASN:可指示普通人肾功能减退风险的蛋白!

2021-09-22 Nebula MedSci原创

可指示普通人肾功能减退风险的蛋白:CLMP、DCTN2、DLK2、DSC2、FSTL3、LMAN2、NBL1、PTGDS、TFF3、TNFRSF1A、TNFRSF1B、WFDC2 和 ZHX3 蛋白

蛋白质组学分析可以识别与肾功能变化相关的血浆蛋白,还可阐明慢性肾病(CKD)发生和进展的生物学过程。

研究人员在社区动脉粥样硬化风险 (ARIC) 研究(中位随访了 14.4 年)的 9406 名参与者(第 3 次随访,平均 60 岁)中量化了 4877 份血浆蛋白与终末期肾病 (ESKD) 或估算的肾小球滤过率(eGFR)下降 ≥50% 的复合结果之间的关联。研究人员还对第 5 次随访的 4378 名参与者子集进行了这些蛋白质的单独分析,这些参与者的随访时间点较晚,中位随访了 4.4 年。

为了进一步验证,研究人员还评估了与在慢性肾功能不全队列(CRIC)的 3249 位参与者和非裔美国人肾脏疾病和高血压研究(AASK)的 703 位参与者在两个时间段内具有显著关联的蛋白质(假发现率 <5%)。研究人员还将蛋白质水平的遗传决定因素与 eGFR 的荟萃分析全基因组关联研究中的因素进行了比较。

ESKD 或 eGFR 下降 ≥50%相关的蛋白

在第 3 次随访队列中,共发生了 595 例终点事件(ESKD 或 eGFR 下降 ≥50%)。在第 5 次随访队列中,共发生了 69 例终点事件。通过根据多个协变量(包括基线 eGFR 和蛋白尿)调整的模型,研究人员确定了 13 个不同的蛋白质,它们在两个时间段都与 ESKD 或 eGFR 下降 ≥50% 的复合终点显著相关,即 CLMP、DCTN2、DLK2、DSC2、FSTL3、LMAN2、NBL1、PTGDS、TFF3、TNFRSF1A、TNFRSF1B、WFDC2 和 ZHX3 蛋白

在这些蛋白中,有 12 个在 CRIC 中与复合终点显著相关,有 9 个在 AASK 中与复合终点显著相关。这些蛋白的任一个水平升高都与 eGFR下降 50% 或 ESKD 的风险更高相关。研究人员还发现了一种蛋白质,即凝集素甘露糖结合 2 蛋白 (LMAN2) 的因果作用的遗传证据。

总而言之,该大规模蛋白质组学分析确定了 eGFR 下降的蛋白质组学风险因素。

原始出处:

Morgan E. Grams, et al. Proteins Associated with Risk of Kidney Function Decline in the General Population. JASN September 2021, 32 (9) 2291-2302; DOI: https://doi.org/10.1681/ASN.2020111607

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    2021-12-29 yese
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    2022-05-29 chenhongpeng
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    2021-09-23 ZYY7209

    不错

    0

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    2021-09-22 ms9000001573448443

    学习

    0

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