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

Mun-Gwan HongTea Dodig-CrnkovicXu ChenKimi DrobinWoojoo LeeYunzhang WangFredrik EdforsDavid KotolCecilia Engel ThomasRonald SjöbergJacob OdebergAnders HamstenAngela SilveiraPer HallPeter NilssonYudi PawitanMathias UhlenNancy L PedersenSara HäggPatrik Ke MagnussonJochen M Schwenk
Published in: Life science alliance (2020)
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 (P = 6.61 × 10-6) 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; P = 6.45 × 10-5) 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.
Keyphrases
  • endothelial cells
  • mass spectrometry
  • risk factors
  • single cell
  • genome wide
  • coronary artery disease
  • high throughput
  • protein protein
  • binding protein
  • dna methylation
  • label free