PMID- 15349727
OWN - NLM
STAT- MEDLINE
DCOM- 20050307
LR  - 20181113
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 47
IP  - 9
DP  - 2004 Sep
TI  - Association between the A-2518G polymorphism in the monocyte chemoattractant 
      protein-1 gene and insulin resistance and Type 2 diabetes mellitus.
PG  - 1574-80
AB  - AIMS/HYPOTHESIS: The molecular mechanisms of obesity-related insulin resistance 
      are incompletely understood. Macrophages accumulate in adipose tissue of obese 
      individuals. In obesity, monocyte chemoattractant protein-1 (MCP-1), a key 
      chemokine in the process of macrophage accumulation, is overexpressed in adipose 
      tissue. MCP-1 is an insulin-responsive gene that continues to respond to 
      exogenous insulin in insulin-resistant adipocytes and mice. MCP-1 decreases 
      insulin-stimulated glucose uptake into adipocytes. The A-2518G polymorphism in 
      the distal regulatory region of MCP-1 may regulate gene expression. The aim of 
      this study was to investigate the impact of this gene polymorphism on insulin 
      resistance. METHODS: We genotyped the Ludwigshafen Risk and Cardiovascular Health 
      (LURIC) cohort ( n=3307). Insulin resistance, estimated by homeostasis model 
      assessment, and Type 2 diabetes were diagnosed in 803 and 635 patients 
      respectively. RESULTS: Univariate analysis revealed that plasma MCP-1 levels were 
      significantly and positively correlated with WHR ( p=0.011), insulin resistance ( 
      p=0.0097) and diabetes ( p<0.0001). Presence of the MCP-1 G-2518 allele was 
      associated with decreased plasma MCP-1 ( p=0.017), a decreased prevalence of 
      insulin resistance (odds ratio [OR]=0.82, 95% CI: 0.70-0.97, p=0.021) and a 
      decreased prevalence of diabetes (OR=0.80, 95% CI: 0.67-0.96, p=0.014). In 
      multivariate analysis, the G allele retained statistical significance as a 
      negative predictor of insulin resistance (OR=0.78, 95% CI: 0.65-0.93, p=0.0060) 
      and diabetes (OR=0.80, 95% CI: 0.66-0.96, p=0.018). CONCLUSIONS/INTERPRETATION: 
      In a large cohort of Caucasians, the MCP-1 G-2518 gene variant was significantly 
      and negatively correlated with plasma MCP-1 levels and the prevalence of insulin 
      resistance and Type 2 diabetes. These results add to recent evidence supporting a 
      role for MCP-1 in pathologies associated with hyperinsulinaemia.
FAU - Simeoni, E
AU  - Simeoni E
AD  - Department of Cardiology, University Hospital, CHUV-BH10, 1011, Lausanne, 
      Switzerland.
FAU - Hoffmann, M M
AU  - Hoffmann MM
FAU - Winkelmann, B R
AU  - Winkelmann BR
FAU - Ruiz, J
AU  - Ruiz J
FAU - Fleury, S
AU  - Fleury S
FAU - Boehm, B O
AU  - Boehm BO
FAU - Marz, W
AU  - Marz W
FAU - Vassalli, G
AU  - Vassalli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040902
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 5Z93L87A1R (Guanine)
RN  - IY9XDZ35W2 (Glucose)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine
MH  - Aged
MH  - Chemokine CCL2/*genetics
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/blood/*genetics
MH  - Female
MH  - Glucose/metabolism
MH  - Guanine
MH  - Homeostasis
MH  - Humans
MH  - Hyperinsulinism/genetics
MH  - Insulin Resistance/*physiology
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/*genetics
EDAT- 2004/09/07 05:00
MHDA- 2005/03/08 09:00
CRDT- 2004/09/07 05:00
PHST- 2004/05/05 00:00 [received]
PHST- 2004/06/18 00:00 [accepted]
PHST- 2004/09/07 05:00 [pubmed]
PHST- 2005/03/08 09:00 [medline]
PHST- 2004/09/07 05:00 [entrez]
AID - 10.1007/s00125-004-1494-4 [doi]
PST - ppublish
SO  - Diabetologia. 2004 Sep;47(9):1574-80. doi: 10.1007/s00125-004-1494-4. Epub 2004 
      Sep 2.