PMID- 20040767
OWN - NLM
STAT- MEDLINE
DCOM- 20100802
LR  - 20220310
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 26
DP  - 2010 Jul 1
TI  - Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating 
      concentrations of monocyte chemoattractant protein-1 and other inflammatory 
      mediators.
PG  - 5289-99
LID - 10.1182/blood-2009-05-221382 [doi]
AB  - To identify the genetic basis of circulating concentrations of monocyte 
      chemoattractant protein-1 (MCP-1), we conducted genome-wide association analyses 
      for MCP-1 in 3 independent cohorts (n = 9598). The strongest association was for 
      serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC, the 
      gene for Duffy antigen receptor for chemokines, a known vascular reservoir of 
      proinflammatory cytokines (minor allele frequency, 45.6%; P < 1.0 * 10(-323)). 
      This association was supported by family-based genetic linkage at a locus 
      encompassing the DARC gene (genome-wide P = 8.0 * 10(-13)). Asp42Gly accounted 
      for approximately 20% of the variability in serum MCP-1 concentrations and also 
      was associated with serum concentrations of interleukin-8 and RANTES. While 
      exploring a lack of association between this polymorphism and EDTA plasma MCP-1 
      concentrations (P = .82), we determined that both clotting and exogenous heparan 
      sulfate (unfractionated heparin) released substantial amounts of MCP-1 from Darc. 
      Quantitative immunoflow cytometry failed to identify meaningful 
      Asp42Gly-associated differences in Darc expression, suggesting that a functional 
      change is responsible for the differential cytokine binding. We conclude that 
      Asp42Gly is a major regulator of erythrocyte Darc-mediated cytokine binding and 
      thereby the circulating concentrations of several proinflammatory cytokines. We 
      have also identified for the first time 2 mechanisms for the release of reservoir 
      chemokines with possible clinical implications.
FAU - Schnabel, Renate B
AU  - Schnabel RB
AD  - National Heart, Lung, and Blood Institute and Boston University Framingham Heart 
      Study, 73 Mount Wayte Avenue ,Framingham, MA 01702-5827, USA.
FAU - Baumert, Jens
AU  - Baumert J
FAU - Barbalic, Maja
AU  - Barbalic M
FAU - Dupuis, Josee
AU  - Dupuis J
FAU - Ellinor, Patrick T
AU  - Ellinor PT
FAU - Durda, Peter
AU  - Durda P
FAU - Dehghan, Abbas
AU  - Dehghan A
FAU - Bis, Joshua C
AU  - Bis JC
FAU - Illig, Thomas
AU  - Illig T
FAU - Morrison, Alanna C
AU  - Morrison AC
FAU - Jenny, Nancy S
AU  - Jenny NS
FAU - Keaney, John F Jr
AU  - Keaney JF Jr
FAU - Gieger, Christian
AU  - Gieger C
FAU - Tilley, Cathy
AU  - Tilley C
FAU - Yamamoto, Jennifer F
AU  - Yamamoto JF
FAU - Khuseyinova, Natalie
AU  - Khuseyinova N
FAU - Heiss, Gerardo
AU  - Heiss G
FAU - Doyle, Margaret
AU  - Doyle M
FAU - Blankenberg, Stefan
AU  - Blankenberg S
FAU - Herder, Christian
AU  - Herder C
FAU - Walston, Jeremy D
AU  - Walston JD
FAU - Zhu, Yanyan
AU  - Zhu Y
FAU - Vasan, Ramachandran S
AU  - Vasan RS
FAU - Klopp, Norman
AU  - Klopp N
FAU - Boerwinkle, Eric
AU  - Boerwinkle E
FAU - Larson, Martin G
AU  - Larson MG
FAU - Psaty, Bruce M
AU  - Psaty BM
FAU - Peters, Annette
AU  - Peters A
FAU - Ballantyne, Christie M
AU  - Ballantyne CM
FAU - Witteman, Jacqueline C M
AU  - Witteman JC
FAU - Hoogeveen, Ron C
AU  - Hoogeveen RC
FAU - Benjamin, Emelia J
AU  - Benjamin EJ
FAU - Koenig, Wolfgang
AU  - Koenig W
FAU - Tracy, Russell P
AU  - Tracy RP
LA  - eng
GR  - UL1RR025005/RR/NCRR NIH HHS/United States
GR  - R21 DA027021/DA/NIDA NIH HHS/United States
GR  - R01 HL104156/HL/NHLBI NIH HHS/United States
GR  - N01-HC-55022/HC/NHLBI NIH HHS/United States
GR  - N01-HC-55016/HC/NHLBI NIH HHS/United States
GR  - DK080739/DK/NIDDK NIH HHS/United States
GR  - N01-HC-55021/HC/NHLBI NIH HHS/United States
GR  - 2K24HL04334/HL/NHLBI NIH HHS/United States
GR  - R01HL087641/HL/NHLBI NIH HHS/United States
GR  - N01-HC-55015/HC/NHLBI NIH HHS/United States
GR  - N01-HC-55020/HC/NHLBI NIH HHS/United States
GR  - HL064753/HL/NHLBI NIH HHS/United States
GR  - 1S10RR163736-01A1/RR/NCRR NIH HHS/United States
GR  - R01 HL077449/HL/NHLBI NIH HHS/United States
GR  - N01-HC-55018/HC/NHLBI NIH HHS/United States
GR  - R01HL086694/HL/NHLBI NIH HHS/United States
GR  - K24 HL105780/HL/NHLBI NIH HHS/United States
GR  - R01HL59367/HL/NHLBI NIH HHS/United States
GR  - AG028321/AG/NIA NIH HHS/United States
GR  - U01HG004402/HG/NHGRI NIH HHS/United States
GR  - HL093328/HL/NHLBI NIH HHS/United States
GR  - N01-HC-55019/HC/NHLBI NIH HHS/United States
GR  - 6R01-NS 17950/NS/NINDS NIH HHS/United States
GR  - HL076784/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20091229
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (ACKR1 protein, human)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Duffy Blood-Group System)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
CIN - Blood. 2010 Jul 1;115(26):5285-6. PMID: 20595521
MH  - Adult
MH  - Chemokine CCL2/*blood/genetics
MH  - Chromosomes, Human, Pair 1
MH  - Cohort Studies
MH  - Duffy Blood-Group System/*genetics/metabolism
MH  - Erythrocytes/metabolism
MH  - Female
MH  - Genetic Loci
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Inflammation Mediators/blood
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, Cell Surface/*genetics/metabolism
PMC - PMC2902130
EDAT- 2009/12/31 06:00
MHDA- 2010/08/03 06:00
PMCR- 2011/07/01
CRDT- 2009/12/31 06:00
PHST- 2009/12/31 06:00 [entrez]
PHST- 2009/12/31 06:00 [pubmed]
PHST- 2010/08/03 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - S0006-4971(20)58377-8 [pii]
AID - 2009/221382 [pii]
AID - 10.1182/blood-2009-05-221382 [doi]
PST - ppublish
SO  - Blood. 2010 Jul 1;115(26):5289-99. doi: 10.1182/blood-2009-05-221382. Epub 2009 
      Dec 29.