Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus.

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.

Hki 27/6 1941

Kirje 27.6.1941

Rouva Annikki Kuuskoski 27/1 1965

Kirje

Presidentti J.K. Paasikivi 27/11 1956

Kirje 27.11.1956

Puheenjohtaja Aarne Saarinen 27/3 1971

Kirje 27.3.1971

Motor Vehicle Crash Fatalities for Week Ending, June 27, 2008

Motor Vehicle Crash Fatalities

Jalkaväenkenraali Yrjö Keinonen 27/1 1969

Kirje 27.1.1969

EPI Update, June 27, 2008

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

Executive Order Number Seven, June 27, 2008

This Executive Order establishes an Iowa Task Force to Rebuild Iowa, after the storms and flood in May and June of 2008.

Kirjailija Sara Ranta-Rönnlund 27/12 1971

Kirje 27.12.1971

Monitoreo oceanográfico pesquero en áreas seleccionadas. MOPAS Chimbote 0112. 27 al 30 de diciembre del 2001

Presenta los resultados del monitoreo oceanográfico pesquero en áreas seleccionadas (MOPAS) realizado por el laboratorio costero de Chimbote, en el área comprendida de Casma y Punta Chérrepe entre el 27 al 30 de diciembre del 2001. Identifica las variables físicas, químicas y biológico-pesqueras y su interrelación para contribuir al aprovechamiento racional de los recursos.