Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Simeoni, E; Hoffmann, MM; Winkelmann, BR; Ruiz, J; Fleury, S; Boehm, BO; März, W; Vassalli, G.
Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus.
Diabetologia. 2004; 47(9):1574-1580
Doi: 10.1007/s00125-004-1494-4
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- Co-Autor*innen der Med Uni Graz
- März Winfried
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenine -
- Aged -
- Chemokine CCL2 - genetics
- Cohort Studies - genetics
- Diabetes Mellitus, Type 2 - blood
- Female - blood
- Glucose - metabolism
- Guanine - metabolism
- Homeostasis - metabolism
- Humans - metabolism
- Hyperinsulinism - genetics
- Insulin Resistance - physiology
- Male - physiology
- Middle Aged - physiology
- Polymorphism, Single Nucleotide - genetics
- Find related publications in this database (Keywords)
- diabetes
- insulin resistance
- macrophage
- monocyte chemoattractant protein-1
- polymorphism