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Polymorphism of the eosinophil cationic protein-gene is related to the expression of allergic symptoms
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2002 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 7, 1092-1095 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We have found a polymorphism in the ECP (eosinophil cationic protein)-gene at position 434 according to GenBank accession number NM 002935. This polymorphism would cause the change of the amino acid arginine (base at position 434 is G) at position 97 to threonine (base at position 434 is C).

OBJECTIVE: To investigate the prevalence of the ECP-polymorphism and to screen for disease associations.

METHODS: DNA of 209 medical students and 76 asthmatic subjects was analysed. The 434 genotype in the ECP-gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis.

RESULTS: The prevalences of the polymorphism in the student population were 53%, 39% and 8% for the 434GG, the 434GC and the 434CC genotype, respectively, with allele frequencies of 72% (434G) and 28% (434C). Subjects reporting allergy had a higher prevalence of the 434G allele than non-allergic subjects (P = 0.0056). Of the students who were Phadiatop-positive and had allergic symptoms, 79% had the 434GG genotype, whereas the 434GC and 434CC genotypes were present in 82% of those who did not express allergic symptoms (P < 0.001). Among the 76 patients with asthma, patients with allergic asthma had a significantly higher proportion of 434GG compared with patients with non-allergic asthma (P = 0.04). None of the 18 subjects of the two groups with the 434CC genotype had allergy.

CONCLUSION: The 434(G > C) polymorphism in the ECP-gene is related to the development of allergic symptoms, suggesting a central role for the ECP molecule in the process.

Place, publisher, year, edition, pages
2002. Vol. 32, no 7, 1092-1095 p.
Keyword [en]
allergy, asthma, DNA, ECP, eosinophil, gene polymorphism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89880DOI: 10.1046/j.1365-2222.2002.01410.xPubMedID: 12100059OAI: oai:DiVA.org:uu-89880DiVA: diva2:161709
Available from: 2002-05-08 Created: 2002-05-08 Last updated: 2010-11-22Bibliographically approved
In thesis
1. Eosinophil Cationic Protein : Expression Levels and Polymorphisms
Open this publication in new window or tab >>Eosinophil Cationic Protein : Expression Levels and Polymorphisms
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The eosinophil cationic protein (ECP) is usually associated with the eosinophil granulocyte. In this thesis the presence and production of this protein has been studied in two other cells. The circulating monocyte was found to contain ECP mRNA and small amounts of ECP, one thousand times less than that found in the eosinophil. The production decreased by differentiation of the myelomonoblastic cell line U937 into a macrophage phenotype. Submucosal lung macrophages did not stain for ECP and alveolar macrophages did not contain ECP mRNA. The circulating neutrophil contains ECP at a level hundred fold less than the eosinophil. We found that the protein is located to the primary granules of the neutrophil but could detect no ECP mRNA in the cell. It was shown in vitro that the protein was taken up by the cell and partly transported to the primary granules. The uptake did not seem to be receptor mediated. Upon stimulation of the neutrophils, ECP previously taken up, was re-secreted.

The ECP protein is heterogeneous both to molecular characteristics and to function. To evaluate if a genetic component is involved, the ECP gene was analysed in 70 individuals. Three single nucleotide polymorphisms (SNP´s) were found, denoted 277(C>T), 434(G>C) and 562(G>C). The two first were located to the mature peptide-coding region and would change the amino acids, arg45cys and arg97thr. The prevalence of the most common SNP, 434, was evaluated in two eosinophil-related diseases, allergy/asthma and Hodgkin Lymphoma (HL). Forty-three HL patients were evaluated and it was found that the 434GG was significantly more prevalent in patients having nodular sclerosis (NS) as compared to other histologies (p=0.03). Erythrocyte sedimentation rate was also related to the 434GG genotype (p=0.009). In 209 medical students 434GG was more common (p=0.002) in those who indicated allergy. The genotype was unrelated to the production of IgE antibodies to allergens. In analysis of 76 subjects with asthma it was found that the 434GG genotype was significantly more common among allergic asthmatics (p=0.04). Asthma and HL-NS are characterized by fibrosis and eosinophils and ECP has been suggested in fibrosis development.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 58 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1161
Medical sciences, Eosinophils, Neutrophils, Monocytes, Macrophages, mRNA, eosinophil cationic protein, DNA, polymorphism, Hodgkin Lymphoma, asthma, allergy, MEDICIN OCH VÅRD
National Category
Medical and Health Sciences
Research subject
Clinical Chemistry
urn:nbn:se:uu:diva-2059 (URN)91-554-5336-8 (ISBN)
Public defence
2002-05-29, Rosénsalen, Uppsala, 13:15
Available from: 2002-05-08 Created: 2002-05-08Bibliographically approved

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