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

C. Szalai, G. Kozma, Adrienne Nagy, Ágnes Bojszkó, Dóra Krikovszky, T. Szabó, A. Falus

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Background: Chemokines play an important role in the pathophysiology of asthma and allergy. Recently, polymorphisms in the gene regulatory region of monocyte chemoattractant protein 1 (MCP-1) and in the promoter region of RANTES have been found; these polymorphisms increase the expression of the chemokines. Objective: We investigated whether the presence of the polymorphisms 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 severity being classified according to the Global Initiative for Asthma guidelines, modified for children), 151 children with nonasthmatic but allergic phenotype, and 303 children without allergic or asthmatic disorders - were screened with a PCR-based assay for genotyping. Results: The frequency of the -2518G polymorphism in the gene regulatory region of MCP-1 was significantly higher in asthmatic children than in controls (P <.001; odds ratio [OR] = 2.0 [1.4-2.6]) and nonasthmatic atopic children (P <.001; OR = 2.0 [1.4-2.9]). The MCP-1 G/G genotype correlated with asthma severity. In asthmatic children, the MCP-1 -2518G allele was also associated with an increased blood eosinophil level. The promoter polymorphisms in the RANTES gene did not have a detectable effect on the susceptibility to asthma or allergy or on the blood eosinophil count. Conclusion: In this cohort of children, there are associations between carrying G at -2518 of the MCP-1 gene regulatory region and the presence of asthma as well as between asthma severity and homozygosity for the G allele. In asthmatic children, the MCP-1-2518G polymorphism correlated with increased eosinophil levels. This variant of MCP-1 might belong to the predictor gene set for asthma.

Original languageEnglish
Pages (from-to)375-381
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume108
Issue number3
DOIs
Publication statusPublished - 2001

Fingerprint

Chemokine CCL2
Nucleic Acid Regulatory Sequences
Asthma
Genes
Eosinophils
Chemokine CCL5
Alleles
Chemokines
Hypersensitivity
Odds Ratio
Genetic Promoter Regions
Genotype
Guidelines
Phenotype
Polymerase Chain Reaction

Keywords

  • Asthma
  • Atopy
  • Chemokines
  • Eosinophils
  • MCP-1
  • Polymorphism
  • RANTES

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. / Szalai, C.; Kozma, G.; Nagy, Adrienne; Bojszkó, Ágnes; Krikovszky, Dóra; Szabó, T.; Falus, A.

In: Journal of Allergy and Clinical Immunology, Vol. 108, No. 3, 2001, p. 375-381.

Research output: Contribution to journalArticle

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AU - Szalai, C.

AU - Kozma, G.

AU - Nagy, Adrienne

AU - Bojszkó, Ágnes

AU - Krikovszky, Dóra

AU - Szabó, T.

AU - Falus, A.

PY - 2001

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N2 - Background: Chemokines play an important role in the pathophysiology of asthma and allergy. Recently, polymorphisms in the gene regulatory region of monocyte chemoattractant protein 1 (MCP-1) and in the promoter region of RANTES have been found; these polymorphisms increase the expression of the chemokines. Objective: We investigated whether the presence of the polymorphisms 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 severity being classified according to the Global Initiative for Asthma guidelines, modified for children), 151 children with nonasthmatic but allergic phenotype, and 303 children without allergic or asthmatic disorders - were screened with a PCR-based assay for genotyping. Results: The frequency of the -2518G polymorphism in the gene regulatory region of MCP-1 was significantly higher in asthmatic children than in controls (P <.001; odds ratio [OR] = 2.0 [1.4-2.6]) and nonasthmatic atopic children (P <.001; OR = 2.0 [1.4-2.9]). The MCP-1 G/G genotype correlated with asthma severity. In asthmatic children, the MCP-1 -2518G allele was also associated with an increased blood eosinophil level. The promoter polymorphisms in the RANTES gene did not have a detectable effect on the susceptibility to asthma or allergy or on the blood eosinophil count. Conclusion: In this cohort of children, there are associations between carrying G at -2518 of the MCP-1 gene regulatory region and the presence of asthma as well as between asthma severity and homozygosity for the G allele. In asthmatic children, the MCP-1-2518G polymorphism correlated with increased eosinophil levels. This variant of MCP-1 might belong to the predictor gene set for asthma.

AB - Background: Chemokines play an important role in the pathophysiology of asthma and allergy. Recently, polymorphisms in the gene regulatory region of monocyte chemoattractant protein 1 (MCP-1) and in the promoter region of RANTES have been found; these polymorphisms increase the expression of the chemokines. Objective: We investigated whether the presence of the polymorphisms 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 severity being classified according to the Global Initiative for Asthma guidelines, modified for children), 151 children with nonasthmatic but allergic phenotype, and 303 children without allergic or asthmatic disorders - were screened with a PCR-based assay for genotyping. Results: The frequency of the -2518G polymorphism in the gene regulatory region of MCP-1 was significantly higher in asthmatic children than in controls (P <.001; odds ratio [OR] = 2.0 [1.4-2.6]) and nonasthmatic atopic children (P <.001; OR = 2.0 [1.4-2.9]). The MCP-1 G/G genotype correlated with asthma severity. In asthmatic children, the MCP-1 -2518G allele was also associated with an increased blood eosinophil level. The promoter polymorphisms in the RANTES gene did not have a detectable effect on the susceptibility to asthma or allergy or on the blood eosinophil count. Conclusion: In this cohort of children, there are associations between carrying G at -2518 of the MCP-1 gene regulatory region and the presence of asthma as well as between asthma severity and homozygosity for the G allele. In asthmatic children, the MCP-1-2518G polymorphism correlated with increased eosinophil levels. This variant of MCP-1 might belong to the predictor gene set for asthma.

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