PMID- 37533140
OWN - NLM
STAT- MEDLINE
DCOM- 20231109
LR  - 20240410
IS  - 1555-905X (Electronic)
IS  - 1555-9041 (Print)
IS  - 1555-9041 (Linking)
VI  - 18
IP  - 11
DP  - 2023 Nov 1
TI  - Differences in the Circulating Proteome in Individuals with versus without Sickle 
      Cell Trait.
PG  - 1416-1425
LID - 10.2215/CJN.0000000000000257 [doi]
AB  - BACKGROUND: Sickle cell trait affects approximately 8% of Black individuals in 
      the United States, along with many other individuals with ancestry from 
      malaria-endemic regions worldwide. While traditionally considered a benign 
      condition, recent evidence suggests that sickle cell trait is associated with 
      lower eGFR and higher risk of kidney diseases, including kidney failure. The 
      mechanisms underlying these associations remain poorly understood. We used 
      proteomic profiling to gain insight into the pathobiology of sickle cell trait. 
      METHODS: We measured proteomics ( N =1285 proteins assayed by Olink Explore) 
      using baseline plasma samples from 592 Black participants with sickle cell trait 
      and 1:1 age-matched Black participants without sickle cell trait from the 
      prospective Women's Health Initiative cohort. Age-adjusted linear regression was 
      used to assess the association between protein levels and sickle cell trait. 
      RESULTS: In age-adjusted models, 35 proteins were significantly associated with 
      sickle cell trait after correction for multiple testing. Several of the sickle 
      cell trait-protein associations were replicated in Black participants from two 
      independent cohorts (Atherosclerosis Risk in Communities study and Jackson Heart 
      Study) assayed using an orthogonal aptamer-based proteomic platform (SomaScan). 
      Many of the validated sickle cell trait-associated proteins are known biomarkers 
      of kidney function or injury ( e.g. , hepatitis A virus cellular receptor 1 
      [HAVCR1]/kidney injury molecule-1 [KIM-1], uromodulin [UMOD], ephrins), related 
      to red cell physiology or hemolysis (erythropoietin [EPO], heme oxygenase 1 
      [HMOX1], and alpha -hemoglobin stabilizing protein) and/or inflammation (fractalkine, 
      C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 [MCP-1], and 
      urokinase plasminogen activator surface receptor [PLAUR]). A protein risk score 
      constructed from the top sickle cell trait-associated biomarkers was associated 
      with incident kidney failure among those with sickle cell trait during Women's 
      Health Initiative follow-up (odds ratio, 1.32; 95% confidence interval, 1.10 to 
      1.58). CONCLUSIONS: We identified and replicated the association of sickle cell 
      trait with a number of plasma proteins related to hemolysis, kidney injury, and 
      inflammation.
CI  - Copyright (c) 2023 by the American Society of Nephrology.
FAU - Cai, Yanwei
AU  - Cai Y
AUID- ORCID: 0000-0002-3950-3794
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, 
      Washington.
FAU - Franceschini, Nora
AU  - Franceschini N
AD  - Department of Epidemiology, Gillings School of Global Public Health, University 
      of North Carolina, Chapel Hill, North Carolina.
FAU - Surapaneni, Aditya
AU  - Surapaneni A
AUID- ORCID: 0000-0003-4978-5980
AD  - Department of Epidemiology and Welch Center for Prevention, Epidemiology, & 
      Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, 
      Maryland.
AD  - Welch Center for Prevention, Epidemiology, & Clinical Research, Johns Hopkins 
      Bloomberg School of Public Health, Baltimore, Maryland.
FAU - Garrett, Melanie E
AU  - Garrett ME
AUID- ORCID: 0000-0003-2302-6150
AD  - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, 
      North Carolina.
FAU - Tahir, Usman A
AU  - Tahir UA
AD  - Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, 
      Boston, Massachusetts.
AD  - Broad Institute of Harvard University and Massachusetts Institute of Technology, 
      Cambridge, Massachusetts.
FAU - Hsu, Li
AU  - Hsu L
AUID- ORCID: 0000-0001-8168-4712
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, 
      Washington.
FAU - Telen, Marilyn J
AU  - Telen MJ
AUID- ORCID: 0000-0003-3809-1780
AD  - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, 
      North Carolina.
AD  - Division of Hematology, Department of Medicine, Duke University Medical Center, 
      Durham, North Carolina.
FAU - Yu, Bing
AU  - Yu B
AUID- ORCID: 0000-0003-4818-1077
AD  - School of Public Health, The University of Texas Health Science Center at 
      Houston, Houston, Texas.
FAU - Tang, Hua
AU  - Tang H
AD  - Department of Genetics, Stanford University School of Medicine, Stanford, 
      California.
FAU - Li, Yun
AU  - Li Y
AUID- ORCID: 0000-0002-9275-4189
AD  - Department of Genetics, University of North Carolina, Chapel Hill, North 
      Carolina.
FAU - Liu, Simin
AU  - Liu S
AUID- ORCID: 0000-0003-2098-3844
AD  - Center for Global Cardiometabolic Health, Departments of Epidemiology, Medicine, 
      and Surgery, Brown University, Providence, Rhode Island.
FAU - Gerszten, Robert E
AU  - Gerszten RE
AUID- ORCID: 0000-0002-6767-7687
AD  - Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, 
      Boston, Massachusetts.
AD  - Broad Institute of Harvard University and Massachusetts Institute of Technology, 
      Cambridge, Massachusetts.
FAU - Coresh, Josef
AU  - Coresh J
AUID- ORCID: 0000-0002-4598-0669
AD  - Department of Epidemiology and Welch Center for Prevention, Epidemiology, & 
      Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, 
      Maryland.
AD  - Welch Center for Prevention, Epidemiology, & Clinical Research, Johns Hopkins 
      Bloomberg School of Public Health, Baltimore, Maryland.
FAU - Manson, JoAnn E
AU  - Manson JE
AUID- ORCID: 0000-0002-9426-7595
AD  - Brigham and Women's Hospital, Harvard Medical School, Harvard T.H. Chan School of 
      Public Health, Boston, Massachusetts.
FAU - Wojcik, Genevieve L
AU  - Wojcik GL
AUID- ORCID: 0000-0001-7206-8088
AD  - Department of Epidemiology and Welch Center for Prevention, Epidemiology, & 
      Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, 
      Maryland.
FAU - Kooperberg, Charles
AU  - Kooperberg C
AD  - Department of Epidemiology, Gillings School of Global Public Health, University 
      of North Carolina, Chapel Hill, North Carolina.
FAU - Auer, Paul L
AU  - Auer PL
AUID- ORCID: 0000-0003-1735-8044
AD  - Division of Biostatistics, Institute for Health and Equity, and Cancer Center, 
      Medical College of Wisconsin, Milwaukee, Wisconsin.
FAU - Foster, Matthew W
AU  - Foster MW
AUID- ORCID: 0000-0003-0212-2346
AD  - Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Duke 
      University Medical Center, Durham, North Carolina.
FAU - Grams, Morgan E
AU  - Grams ME
AUID- ORCID: 0000-0002-4430-6023
AD  - Division of Precision Medicine, New York University Grossman School of Medicine, 
      New York, New York.
FAU - Ashley-Koch, Allison E
AU  - Ashley-Koch AE
AUID- ORCID: 0000-0001-5409-9155
AD  - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, 
      North Carolina.
FAU - Raffield, Laura M
AU  - Raffield LM
AUID- ORCID: 0000-0002-7892-193
AD  - Department of Genetics, University of North Carolina, Chapel Hill, North 
      Carolina.
FAU - Reiner, Alex P
AU  - Reiner AP
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, 
      Washington.
AD  - Department of Epidemiology, University of Washington, Seattle, Washington.
LA  - eng
GR  - HHSN268201100037C/HL/NHLBI NIH HHS/United States
GR  - 75N92021D00002/HL/NHLBI NIH HHS/United States
GR  - 75N92021D00005/WH/WHI NIH HHS/United States
GR  - HHSN268201800014I/HB/NHLBI NIH HHS/United States
GR  - U01-HG011720/HG/NHGRI NIH HHS/United States
GR  - HHSN268201800014C/HL/NHLBI NIH HHS/United States
GR  - 75N92021D00001/HL/NHLBI NIH HHS/United States
GR  - 75N92021D00003/WH/WHI NIH HHS/United States
GR  - R01-MD012765/MD/NIMHD NIH HHS/United States
GR  - HHSN268201800015I/HB/NHLBI NIH HHS/United States
GR  - R01 MD012765/MD/NIMHD NIH HHS/United States
GR  - HHSN268201800010I/HB/NHLBI NIH HHS/United States
GR  - R01 HL117626/HL/NHLBI NIH HHS/United States
GR  - HHSN268201800011I/HB/NHLBI NIH HHS/United States
GR  - 75N92021D00004/WH/WHI NIH HHS/United States
GR  - HHSN268201800012I/HB/NHLBI NIH HHS/United States
GR  - HHSN268201800012C/HL/NHLBI NIH HHS/United States
GR  - R01 HL120393/HL/NHLBI NIH HHS/United States
GR  - R01 HL152439/HL/NHLBI NIH HHS/United States
GR  - U01 HL120393/HL/NHLBI NIH HHS/United States
GR  - R01 DK117445/DK/NIDDK NIH HHS/United States
GR  - HHSN268201800001C/HL/NHLBI NIH HHS/United States
GR  - U01 HG011720/HG/NHGRI NIH HHS/United States
GR  - HHSN268201800013I/MD/NIMHD NIH HHS/United States
GR  - R01-DK117445/DK/NIDDK NIH HHS/United States
GR  - HHSN268201800011C/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230803
PL  - United States
TA  - Clin J Am Soc Nephrol
JT  - Clinical journal of the American Society of Nephrology : CJASN
JID - 101271570
RN  - 0 (Proteome)
RN  - 0 (Biomarkers)
SB  - IM
CIN - Clin J Am Soc Nephrol. 2023 Nov 1;18(11):1391-1392. PMID: 37783470
MH  - Humans
MH  - Female
MH  - United States
MH  - *Sickle Cell Trait
MH  - Proteome
MH  - Prospective Studies
MH  - Hemolysis
MH  - Proteomics
MH  - Biomarkers
MH  - *Renal Insufficiency
MH  - Inflammation
PMC - PMC10637465
COIS- J. Coresh consultancy for Healthy.io and SomaLogic, ownership interest in 
      Healthy.io, research funding from the National Institute of Health and National 
      Kidney Foundation, and an advisory or leadership role for SomaLogic. M.W. Foster 
      reports research funding from Biomilq, Circumvent Pharmaceuticals, and Oerth Bio. 
      N. Franceschini reports advisory or leadership roles for Women's Health 
      Initiative Chair of Ancillary Committee and Women's Health Initiative Publication 
      and Presentation Committee. M.E. Grams reports advisory or leadership roles for 
      the American Journal of Kidney Diseases, ASN Publication Committee, CJASN, JASN 
      Editorial Fellowship Committee, KDIGO Executive Committee (co-chair elect), NKF 
      Scientific Advisory Board, and USRDS Scientific Advisory Board; grant funding 
      from NKF, which receives funding from multiple pharmaceutical companies; grant 
      funding from NIH; payment from academic institutions for grand rounds; and 
      payment from NephSAP. S. Liu reports consultancy for Novo Nordisk and TwinHealth. 
      J.E. Manson reports research funding from Mars Edge. L.M. Raffield reports 
      consultancy for TOPMed Administrative Coordinating Center (through Westat). M.J. 
      Telen reports consultancy from Novartis and Pfizer, Inc.; research funding from 
      BioMedomics, CSL Behring, NIH, Novartis, Novo Nordisk, and Pfizer; and honoraria 
      from Novartis and Pfizer. All remaining authors have nothing to disclose.
EDAT- 2023/08/03 06:42
MHDA- 2023/11/09 06:42
PMCR- 2024/11/01
CRDT- 2023/08/03 00:03
PHST- 2023/03/25 00:00 [received]
PHST- 2023/07/26 00:00 [accepted]
PHST- 2024/11/01 00:00 [pmc-release]
PHST- 2023/11/09 06:42 [medline]
PHST- 2023/08/03 06:42 [pubmed]
PHST- 2023/08/03 00:03 [entrez]
AID - 01277230-202311000-00008 [pii]
AID - CJASN-2023-000404 [pii]
AID - 10.2215/CJN.0000000000000257 [doi]
PST - ppublish
SO  - Clin J Am Soc Nephrol. 2023 Nov 1;18(11):1416-1425. doi: 
      10.2215/CJN.0000000000000257. Epub 2023 Aug 3.