Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 −2518 G/G genotype in CAD patients

Szalai, Csaba; Duba, J.; Prohászka, Zoltán; Kalina, Ákos; Szabó, T; Nagy, Béla; Horváth, Laura; Császár, Albert

doi:10.1016/s0021-9150(01)00423-3

Cited by 284 publications

(207 citation statements)

References 30 publications

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“…Moreover, MCP-1 expression in isolated, cytokine-stimulated human peripheral blood mononuclear cells [22,25] and hepatic cells [26], and plasma MCP-1 levels in patients with lupus nephritis support the assumption that the gene polymorphism regulates MCP-1 expression at the transcriptional level [25]. Case-control gene association studies have reported statistical associations between the polymorphism and lupus nephritis [25], coronary artery disease (CAD) [27] and asthma [28]. The aim of the present study was to test the hypothesis that the MCP-1 A-2518G polymorphism influences plasma MCP-1 levels and the risk of developing insulin resistance and Type 2 diabetes.…”

Section: Introductionmentioning

confidence: 80%

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

et al. 2004

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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, p=0.0060) and diabetes (OR=0.80, 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.

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Section: Introductionmentioning

confidence: 80%

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

et al. 2004

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“…The rare Val64Ile polymorphism in the CCR2 gene was associated with reduced coronary calcification, as well as MCP-1 G2518 homozygosity [36,37]. On the contrary Brenner et al demonstrated a A2518 association with increased IMT [38].…”

Section: Discussionmentioning

confidence: 99%

Genetic control of chemokines in severe human internal carotid artery stenosis

et al. 2008

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Background and purpose: Atherosclerosis is an inflammatory disease. Chemokines and chemokine receptors are known to be involved in atherogenesis. Common single nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory stimuli. The aim of this study was to evaluate the correlations between MCP-1, RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal carotid artery (ICA) stenosis. Methods: Hundred and twelve patients, consecutively recruited for ICA occlusive disease, and 282 controls were genotyped for MCP-1-2518G, RANTES-403A, CCR5D32, CCR2 V64I, and SDF-1-801A polymorphisms. Results: The frequency of the SDF-1A allele was significantly different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95% CI 1.25-2.60; p = 0.007). The frequency of the RANTES-403G allele was significantly higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12-5.71; p = 0.015). No significant differences were observed with the other polymorphisms. Conclusion:The reported results seem to correlate the polymorphisms of the genes encoding for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease. Although suggestive, these results need confirmation in prospective cross-sectional studies.

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“…The SDF-1 3'A variant (801G to A in the 3'-untranslated region) was detected by electrophoresis on 2.5% agarose gel after PCR amplification and MspI (New England Biolabs, SaintQuentin-en-Yvelines, France) digestion as previously described [16] . Genotype analysis for MCP-1 (-2518) was performed on genomic DNA with PCR with sequencespecific primers followed by restriction fragment length polymorphism analysis as described [22,23] . Briefly, after PCR amplification, PCR products were digested with PvuⅡ (recognizes the MCP-1 -2518 A/G transition) (New England Biolabs).…”

Section: Follow-upmentioning

confidence: 99%

Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis

Nahon¹

2008

WJG

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Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 −2518 G/G genotype in CAD patients

Cited by 284 publications

References 30 publications

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

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

Genetic control of chemokines in severe human internal carotid artery stenosis

Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis

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