Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity

Szalai, Csaba; Kozma, Gergely Tibor; Nagy, Adrienne; Bojszkó, Ágnes; Krikovszky, Dóra; Szabó, T; Falus, András

doi:10.1067/mai.2001.117930

Cited by 161 publications

(122 citation statements)

References 31 publications

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“…In contrast to our results, the CCL2-2578G allele frequency was more frequent in subjects with asthma than in control subjects in two studies of Hungarian populations, 15,16 one of which also found the CCL2-2578G allele to be associated with asthma severity. 15 Furthermore, a Chinese case-control study did not detect any association with childhood asthma. 17 Possible explanations for these discrepancies among the different studies include the inclusion criteria, origins of the study populations and small sample sizes.…”

Section: Discussioncontrasting

confidence: 99%

“…A polymorphism in the distal regulatory region of the CC chemokine ligand-2 (CCL2) gene (CCL2-G2578) modulates CCL2 production, 12,13 and is associated with a reduced risk of severe coronary artery diseases. 14 Two independent studies in Hungary reported that the chemokine CCL2-2578G allele is more frequent in children with asthma than in controls 15,16 although a study in northern Taiwan could not replicate these findings. 17 CC chemokine receptor-2 (CCR2), the only known receptor for CCL2, is another candidate gene for asthma.…”

Section: Introductionmentioning

confidence: 98%

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A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

et al. 2008

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Asthma is a complex genetic disorder characterized by chronic airway inflammation. We hypothesized that genetic polymorphisms in chemokines and their receptors alter leukocyte mobilization and may thus influence the risk and severity of childhood asthma. Distributions of the chemokine CCL2-2578G, CCL2-927C, CCR2-V64I, CX3CR1-V249I and CX3CR1-T280M receptor polymorphisms were examined in a case-control study of 121 children with asthma and 226 age-matched healthy controls and then replicated in a family study of 99 simplex families (297 individuals). The case-control study revealed that the CCL2-2578G allele was less frequent in children with than in those without asthma (P ¼ 0.0012). No association with asthma was found for the CCL2-927, CCR2 or CX3CR1 polymorphisms. The finding in the family study that the CCL2-2578G allele was transmitted less often by heterozygous parents to their children with asthma (P ¼ 0.0016) confirms the association of CCL2-2578G with asthma risk. Biochemical studies indicated that plasma CCL2 concentrations were higher in both patients (P ¼ 0.0214) and controls (P ¼ 0.001) carrying the G allele than in subjects with other polymorphisms. Both case-control and family-based studies suggest a protective effect of allele CCL2-2578G in Tunisian asthmatic children.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 98%

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

et al. 2008

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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: 76%

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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“…A recent study has shown that an increase in the frequency of asthma was associated with the G allele. 27 The reasons for the differences in cytokine production in infants and the subsequent development of CLD are not completely understood and are undoubtedly multifactorial. Differences in ventilation strategies, lung maturity, pre-and postnatal infections, nutritional status and genetic factors (presumably) interact in the development of CLD.…”

Section: Introductionmentioning

confidence: 99%

The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

et al. 2003

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Chronic lung disease (CLD) in premature newborns is associated with increased concentrations of inflammatory cytokines in tracheal aspirates (TA). We determined if polymorphisms of cytokine genes influence the risk of developing CLD by genotyping 178 mechanically ventilated very low birth weight (VLBW) infants for the tumor necrosis factor-a (TNF-a) À308 G/A, transforming growth factor-b 1 (TGF-b 1 ) +915 G/C and monocyte chemoattractant protein-1 (MCP-1) À2518 A/G polymorphisms. Genomic DNA was isolated from TA and genotypes determined by restriction length polymorphism. There was no effect of any of these polymorphisms on the development of CLD (29 vs 23%, P ¼ 0.371, TNF-a À308 AA/AG vs TNF-a À308 GG; 23 vs 26%, P ¼ 0.681, MCP-1 À2518 GG/AG vs MCP-1 À215-8 AA; 24 vs 24%, P ¼ 0.978, TGF-b 1 +915 CG vs TGF-b 1 +915 GG). TA IL-8 and MCP-1 concentrations were not different between genotype groups. Infants with the TNF-a À308 A allele had increased risk of IVH (RR 2.07; 95% CI 1.02-4.18, P ¼ 0.041) and infants with the TGF-b 1 +915 C allele were at greater risk of death (32 vs 9%, P ¼ 0.016). These data suggest that these polymorphisms do not play a significant role in determining risk for CLD in preterm infants, but may play a role in other complications in the neonatal period.

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Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity

Cited by 161 publications

References 31 publications

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

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

The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

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