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

Background: Chemokines play an important role in the pathophysiology of ast hma and allergy. Recently, polymorphisms in the gene regulatory region of m onocyte chemoattractant protein 1 (MCP-1) and in the promoter region of RAN TES have been found; these polymorphisms increase the expression of the che mokines. Objective: We investigated whether the presence of the polymorphis ms was associated with atopy or asthma and whether these alleles influenced the severity of asthma in affected individuals. Methods: Three groups of subjects-160 children with asthma (disease severit y being classified according to the Global Initiative for Asthma guidelines , modified for children), 151 children with nonasthmatic but allergic pheno type, and 303 children without allergic or asthmatic disorders-were screene d with a PCR-based assay for genotyping. Results: The frequency of the -2518G polymorphism in the gene regulatory re gion of MCP-I was significantly higher in asthmatic children than in contro ls (P < .001; odds ratio [OR] = 2.0 [1.4-2.6]) and nonasthmatic atopic chil dren (P < .00 1; OR = 2.0 [1.4-2.9]). The MCP-1 G/G genotype correlated wit h asthma severity. In asthmatic children, the MCP-1 -2518G allele was also associated with an increased blood eosinophil level. The promoter polymorph isms in the RANTES gene did not have a detectable effect on the susceptibil ity to asthma or allergy or on the blood eosinophil count. Conclusion: In this cohort of children, there are associations between carr ying G at -2518 of the MCP-1 gene regulatory region and the presence of ast hma as well as between asthma severity and homozygosity for the G allele. I n asthmatic children, the MCP-1-2518G polymorphism correlated with increase d eosinophil levels. This variant of MCP-1 might belong to the predictor ge ne set for asthma.