A Novel Polymorphism in the MCP-1 Gene Regulatory Region That Influences MCP-1 Expression

Rovin, Brad H.; Lu, Ling; Saxena, Ramesh

doi:10.1006/bbrc.1999.0796

Cited by 423 publications

(428 citation statements)

References 25 publications

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“…A common A→G polymorphism located at position −2518 in the distal regulatory region regulates MCP-1 expression. This was demonstrated by transfection experiments in A172 and 293T cells using reporter gene constructs containing the distal regulatory region of the MCP-1 gene with either variant at position −2518 [22,25]. 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].…”

Section: Introductionmentioning

confidence: 62%

“…In search of genetic factors that affect insulin resistance, we investigated the role of the common MCP-1 A-2518G polymorphism, which may regulate MCP-1 expression at the transcriptional level [22,25,26]. In a large cohort of Caucasians with a high prevalence of cardiovascular risk factors, we found decreased plasma MCP-1 levels and a decreased prevalence of insulin resistance and Type 2 diabetes in carriers of the G allele compared with subjects homozygous for the frequent A allele.…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping of the MCP-1 A-2518G polymorphism was carried out by RFLP-PCR as described previously [22]. Data are incomplete due to missing or equivocal results in five subjects.…”

Section: Study Population and Clinical Definitionsmentioning

confidence: 99%

“…This was demonstrated by transfection experiments in A172 and 293T cells using reporter gene constructs containing the distal regulatory region of the MCP-1 gene with either variant at position −2518 [22,25]. 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].…”

Section: Introductionmentioning

confidence: 99%

“…Substantial interindividual variability in MCP-1 production in response to proinflammatory cytokines has previously been described [22,23]. Human MCP-1 transcription is under the control of two distinct regions within the 5'-flanking sequence of the gene.…”

Section: Introductionmentioning

confidence: 99%

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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: 62%

Section: Discussionmentioning

confidence: 99%

“…Genotyping of the MCP-1 A-2518G polymorphism was carried out by RFLP-PCR as described previously [22]. Data are incomplete due to missing or equivocal results in five subjects.…”

Section: Study Population and Clinical Definitionsmentioning

confidence: 99%