PT  - JOURNAL ARTICLE
AU  - Hong, Mun-Gwan
AU  - Dodig-Crnković, Tea
AU  - Chen, Xu
AU  - Drobin, Kimi
AU  - Lee, Woojoo
AU  - Wang, Yunzhang
AU  - Edfors, Fredrik
AU  - Kotol, David
AU  - Thomas, Cecilia Engel
AU  - Sjöberg, Ronald
AU  - Odeberg, Jacob
AU  - Hamsten, Anders
AU  - Silveira, Angela
AU  - Hall, Per
AU  - Nilsson, Peter
AU  - Pawitan, Yudi
AU  - Uhlén, Mathias
AU  - Pedersen, Nancy L
AU  - Hägg, Sara
AU  - Magnusson, Patrik KE
AU  - Schwenk, Jochen M
TI  - Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
AID  - 10.26508/lsa.202000817
DP  - 2020 Oct 01
TA  - Life Science Alliance
PG  - e202000817
VI  - 3
IP  - 10
4099  - http://www.life-science-alliance.org/content/3/10/e202000817.short
4100  - http://www.life-science-alliance.org/content/3/10/e202000817.full
SO  - Life Sci. Alliance2020 Oct 01; 3
AB  - 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.