The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE

Kim, Hyun Lee; Lee, Dong Sup; Yang, Seung Hee; Lim, Chun Soo; Chung, Jong Hoon; Kim, Sejoong; Lee, Jung Sang; Kim, Yon Su

doi:10.1053/ajkd.2002.36858

Cited by 94 publications

(72 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 63%

“…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%

“…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%

“…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: 99%

See 3 more Smart Citations

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

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Genomic DNA was extracted from the peripheral blood of all subjects, using the QIAamp Blood kit (Qiagen, Valencia, CA). Genotyping was carried out in accordance with published methods (12)(13)(14)(15)(16)(17). A polymerase chain reaction (PCR)-sequence-specific primer method was used to genotype CXCR1 ϩ827 G/C and CXCR2 ϩ786 C/T, while a PCR-restriction fragment length polymorphism method was used to genotype CXCL8 (interleukin-…”

Section: Methodsmentioning

confidence: 99%

Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Lee¹,

Zhao²,

Kim³

et al. 2007

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).Methods. To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age-and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reactionrestriction fragment length polymorphism or sequencespecific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chisquare tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.Results. There was significant evidence of genegene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.Conclusion. Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.

show abstract

Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis

Tucci¹,

Barnes²,

Sobel³

et al. 2004

Arthritis & Rheumatism

121

View full text Add to dashboard Cite

Objective. Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is evidence that polymorphisms in the genes of inflammatory mediators may predispose to the development of LN in patients with SLE. In this study, we examined the role of a functional monocyte chemoattractant protein 1 (MCP-1) polymorphism in SLE and LN.Methods. DNA and paired urine and serum samples were obtained from 134 SLE patients (>4 American College of Rheumatology criteria for SLE; 49 with and 85 without LN) and 118 controls. MCP-1 genomic variants were detected by polymerase chain reaction followed by restriction enzyme-fragment analysis. Urinary and serum MCP-1 levels and MCP-1 production by peripheral blood macrophages were measured by enzyme-linked immunosorbent assay.Results. The A/A genotype was more common in controls than in SLE patients (P ‫؍‬ 0.0002), whereas both the A/G (P ‫؍‬ 0.009) and G/G (P ‫؍‬ 0.0212) genotypes were more frequent in SLE patients. The A/A genotype was observed in only 23% of the patients with LN compared with 58% of those without LN (P < 0.0001). MCP-1 production by peripheral blood mononuclear cells from patients with the A/G and G/G phenotypes was markedly higher than the production by cells from patients with the A/A genotype. Urinary levels of MCP-1 were significantly higher in patients with LN.Conclusion. These results suggest that an A/G or G/G genotype may predispose to the development of SLE and further indicate that SLE patients with these genotypes may be at higher risk of developing LN. Moreover, measurement of urinary levels of MCP-1 may be a useful tool for the detection and management of LN.

show abstract

The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE

Cited by 94 publications

References 19 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

Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis

Contact Info

Product

Resources

About