PMID- 17767550
OWN - NLM
STAT- MEDLINE
DCOM- 20071127
LR  - 20161124
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 70
IP  - 4
DP  - 2007 Oct
TI  - Elevated MCP-1 serum levels are associated with the H63D mutation and not the 
      C282Y mutation in hereditary hemochromatosis.
PG  - 294-300
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a major lymphocyte and inflammatory 
      chemokine associated with persistent inflammatory states. Several abnormalities 
      in the immune status of patients with hereditary hemochromatosis (HH) have been 
      reported, suggesting an imbalance in their immune function. This may include 
      persistent production of, or exposure to, inflammatory cytokines contributing to 
      the pathogenesis of this disorder. The aim of this study was to assess MCP-1 
      levels in patients with HH and correlate these results with HFE status and iron 
      indexes. One hundred and thirty-nine subjects diagnosed with HH (C282Y 
      homozygotes = 87, C282Y/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 
      healthy control subjects with no HFE mutation (N/N), and 18 normal subjects 
      heterozygous for the H63D mutation served as age- and sex-matched controls. 
      Ferritin and transferrin saturation and the presence of HFE mutation status were 
      correlated with MCP-1 levels. Full white blood cell count analysis was also 
      performed. We found a strongly significant decrease in MCP-1 protein levels in 
      the C282Y homozygotes compared with the H63D homozygotes (P = 0.0009) and 
      C282Y/H63D heterozygotes (P = 0.002). Similarly, MCP-1 protein levels in the 
      C282Y homozygotes were decreased compared with the healthy controls (P = 
      0.00076). Furthermore, MCP-1 serum levels were elevated in H63D patients compared 
      with the healthy controls (P = 0.0008). This study suggests for the first time 
      that a differential expression of MCP-1 protein in patients with HH is associated 
      with the specific HFE genetic component for iron overload. Therefore, these 
      findings offer a possible explanation in the variable clinical spectrum of 
      pathogenesis in patients with HH through abnormalities of an imbalance in the 
      immune states of patients with HH.
FAU - Lawless, M W
AU  - Lawless MW
AD  - Hepatology Research Division and Department of Clinical Medicine, Institute of 
      Molecular Medicine, Trinity College Dublin, St James Hospital, Dublin 8, Ireland. 
      mlawles@tcd.ie
FAU - White, M
AU  - White M
FAU - Mankan, A K
AU  - Mankan AK
FAU - O'Dwyer, M J
AU  - O'Dwyer MJ
FAU - Norris, S
AU  - Norris S
LA  - eng
PT  - Journal Article
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (HFE protein, human)
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
RN  - 0 (Transferrin)
RN  - 9007-73-2 (Ferritins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chemokine CCL2/*blood
MH  - Female
MH  - Ferritins/blood
MH  - Hemochromatosis/*blood/*genetics
MH  - Hemochromatosis Protein
MH  - Heterozygote
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Homozygote
MH  - Humans
MH  - Iron/blood
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - Mutation
MH  - Transferrin/analysis
EDAT- 2007/09/05 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/09/05 09:00
PHST- 2007/09/05 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/09/05 09:00 [entrez]
AID - TAN895 [pii]
AID - 10.1111/j.1399-0039.2007.00895.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2007 Oct;70(4):294-300. doi: 10.1111/j.1399-0039.2007.00895.x.