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富含组氨酸的糖蛋白的特征与年龄和全因死亡率的风险相关。

Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality.

机构信息

Department of Protein Science, Science for Life Laboratory, KTH-Royal Institute of Technology, Solna, Sweden.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

出版信息

Life Sci Alliance. 2020 Jul 31;3(10). doi: 10.26508/lsa.202000817. Print 2020 Oct.

DOI:10.26508/lsa.202000817
PMID:32737166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7409555/
Abstract

Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50-92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association ( = 6.61 × 10) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12-1.39; = 6.45 × 10) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7-9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.

摘要

尽管人们认识到衰老作为许多人类疾病的共同风险因素，但对其分子特征知之甚少。为了鉴定在人类血液中循环的与年龄相关的蛋白质，我们使用探索性和多重亲和蛋白质组学测定法筛选了 156 名年龄在 50-92 岁的个体。对另外 8 个研究组（N=3987）进行分析，进行抗体验证，并进行荟萃分析，揭示了循环组氨酸丰富糖蛋白（HRG）与年龄之间的一致相关性（=6.61×10）。HRG 的序列变异影响了该蛋白在免疫测定中的识别方式。事实上，只有受 rs9898 影响的 HRG 图谱与年龄相关，并预测了死亡率风险（HR=1.25/SD；95%CI=1.12-1.39；=6.45×10），在采血后 8.5 年的随访期间（IQR=7.7-9.3 年）。我们的亲和蛋白质组学分析发现，循环 HRG 的特定分子特征与年龄和全因死亡率之间存在关联。这种多功能蛋白质的独特图谱可以作为与生物衰老相关的生理过程的一种易于获取且信息丰富的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/5740a299445b/LSA-2020-00817_FigS9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/5740a299445b/LSA-2020-00817_FigS9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/9ff48614c588/LSA-2020-00817_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/e33b1d0a0566/LSA-2020-00817_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/f2dae92c4a62/LSA-2020-00817_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/1834b3e68caa/LSA-2020-00817_Fig2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9325/7409555/efb018f3733f/LSA-2020-00817_Fig3.jpg
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