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

Abstract

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.

miR-511-3p protects against cockroach allergen–induced lung inflammation by antagonizing CCL2

“…Of these, Ccl2 belongs to the C-C class of chemokines and has been shown to be a key modulator of inflammation, with specific chemotactic activity for monocytes/macrophages via preferential interaction with Ccr2 (40,41). Alterations in the expression of CCL2 have been observed in BAL fluids from allergen-challenged asthmatic patients (24), and demonstrated its association with asthma (42)(43)(44). Thus, we prioritized Ccl2 as a potentially novel target gene for miR-511-3p that may participate in miR-511-3p-regulated downstream immune responses in allergic asthma.…”

CCL2/CCR2-Dependent Recruitment of Th17 Cells but Not Tc17 Cells to the Lung in a Murine Asthma Model

“…Accumulating evidence [9,10,11,12] indicates that CCL2 plays an important role in asthma. Asthma patients have significantly higher serum CCL2 levels than normal controls in the asymptomatic phase of the disease and also during an acute asthma attack [13].…”

Association between MCP-1 -2518A>G polymorphism and asthma susceptibility: a meta-analysis

“…They found that the MCP-1 -2518 G polymorphism was correlated with asthma severity, and their results were subsequently supported by Keszei et al (15) and Tolgyesi et al (16). In contrast, two studies reported a protective effect of allele MCP-1 -2518 G polymorphism in asthmatic children (17,18), and three studies showed no significant association between MCP-1 -2518 G polymorphism and asthma risk (13,14,19). Our meta-analysis provided a more precise estimation based on a larger sample size compared with the individual study.…”

“…Interestingly, the heterogeneity was dramatically reduced or disappeared from the Caucasian subgroup after ethnicity subgroup analysis, and the subgroup pooled results showed an increased risk of asthma with MCP-1 -2518 G polymorphism in the Caucasian population, a protective effect for MCP-1 -2518 G polymorphism in the African population under the dominant model, and no significant association in the Asian population. Accordingly, the mean plasma MCP-1 protein level was significantly lower in the asthmatic than in the control children from Hungary (15), but plasma MCP-1 protein level was higher in the asthmatic than in the control children from Tunisia (17). The possible explanation is that the genetic variation in the MCP-1 promoter region not only affects the production of MCP-1, but also affects the secretion of MCP-1.…”