Variant eotaxin: Its effects on the asthma phenotype

Hidetoshi Nakamura, Andrew D. Luster, Toshiko Nakamura, Kwang Ho In, Larry A. Sonna, Aaron Deykin, Elliot Israel, Jeffrey M. Drazen, Craig M. Lilly

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background: Eotaxin, a CC chemokine expressed in the asthmatic lung, has been associated with impaired lung function. The role of its variant form is unknown. Objective: The purpose of this study was to detect the population frequency and effects of a known single-nucleotide polymorphism in the eotaxin gene in which a threonine residue (THR23) is substituted for the wild-type alanine (ALA23) at the 23rd amino acid at the terminus of the peptide leader sequence. Methods: We measured eotaxin protein secretion in 293 cells transfected with expression vectors and in PBMCs obtained from individuals bearing the alternative forms of the gene. A case-control study of plasma eotaxin levels and eosinophil counts, a comparison of baseline lung function by genotype in a population of 806 subjects with asthma, and a comparison of the allele frequency with a nonasthmatic population were performed. Results: Human 293 cells and PBMCs with THR23 variant eotaxin secreted significantly less eotaxin protein than did ALA23-bearing cells. In the case-control study, THR23-THR23 individuals had lower plasma levels of eotaxin (310[240-350] vs 420 [270-700] pg/mL; P < .05) and eosinophil counts (120[5-220] vs 190 [110-470] cells/μL; P < .05) than ALA23-ALA23 subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR23 eotaxin (percent of predicted FEV1 65% ± 3.5% [THR23-THR23] vs 58% ± 0.9% [THR23-ALA23] and 56% ± 0.5% [ALA23-ALA23]; P < .05). Conclusion: The THR23 variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma.

Original languageEnglish
Article number15482
Pages (from-to)946-953
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume108
Issue number6
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Fingerprint

Asthma
Phenotype
Lung
Eosinophils
Case-Control Studies
Population
CC Chemokines
Threonine
Protein Sorting Signals
Gene Frequency
Alanine
Genes
Single Nucleotide Polymorphism
Proteins
Genotype
Amino Acids

Keywords

  • Asthma
  • Chemokines
  • Eotaxin
  • Human genetics
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Nakamura, H., Luster, A. D., Nakamura, T., In, K. H., Sonna, L. A., Deykin, A., ... Lilly, C. M. (2001). Variant eotaxin: Its effects on the asthma phenotype. Journal of Allergy and Clinical Immunology, 108(6), 946-953. [15482]. https://doi.org/10.1067/mai.2001.120135

Variant eotaxin : Its effects on the asthma phenotype. / Nakamura, Hidetoshi; Luster, Andrew D.; Nakamura, Toshiko; In, Kwang Ho; Sonna, Larry A.; Deykin, Aaron; Israel, Elliot; Drazen, Jeffrey M.; Lilly, Craig M.

In: Journal of Allergy and Clinical Immunology, Vol. 108, No. 6, 15482, 01.01.2001, p. 946-953.

Research output: Contribution to journalArticle

Nakamura, H, Luster, AD, Nakamura, T, In, KH, Sonna, LA, Deykin, A, Israel, E, Drazen, JM & Lilly, CM 2001, 'Variant eotaxin: Its effects on the asthma phenotype', Journal of Allergy and Clinical Immunology, vol. 108, no. 6, 15482, pp. 946-953. https://doi.org/10.1067/mai.2001.120135
Nakamura H, Luster AD, Nakamura T, In KH, Sonna LA, Deykin A et al. Variant eotaxin: Its effects on the asthma phenotype. Journal of Allergy and Clinical Immunology. 2001 Jan 1;108(6):946-953. 15482. https://doi.org/10.1067/mai.2001.120135
Nakamura, Hidetoshi ; Luster, Andrew D. ; Nakamura, Toshiko ; In, Kwang Ho ; Sonna, Larry A. ; Deykin, Aaron ; Israel, Elliot ; Drazen, Jeffrey M. ; Lilly, Craig M. / Variant eotaxin : Its effects on the asthma phenotype. In: Journal of Allergy and Clinical Immunology. 2001 ; Vol. 108, No. 6. pp. 946-953.
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abstract = "Background: Eotaxin, a CC chemokine expressed in the asthmatic lung, has been associated with impaired lung function. The role of its variant form is unknown. Objective: The purpose of this study was to detect the population frequency and effects of a known single-nucleotide polymorphism in the eotaxin gene in which a threonine residue (THR23) is substituted for the wild-type alanine (ALA23) at the 23rd amino acid at the terminus of the peptide leader sequence. Methods: We measured eotaxin protein secretion in 293 cells transfected with expression vectors and in PBMCs obtained from individuals bearing the alternative forms of the gene. A case-control study of plasma eotaxin levels and eosinophil counts, a comparison of baseline lung function by genotype in a population of 806 subjects with asthma, and a comparison of the allele frequency with a nonasthmatic population were performed. Results: Human 293 cells and PBMCs with THR23 variant eotaxin secreted significantly less eotaxin protein than did ALA23-bearing cells. In the case-control study, THR23-THR23 individuals had lower plasma levels of eotaxin (310[240-350] vs 420 [270-700] pg/mL; P < .05) and eosinophil counts (120[5-220] vs 190 [110-470] cells/μL; P < .05) than ALA23-ALA23 subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR23 eotaxin (percent of predicted FEV1 65{\%} ± 3.5{\%} [THR23-THR23] vs 58{\%} ± 0.9{\%} [THR23-ALA23] and 56{\%} ± 0.5{\%} [ALA23-ALA23]; P < .05). Conclusion: The THR23 variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma.",
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AU - In, Kwang Ho

AU - Sonna, Larry A.

AU - Deykin, Aaron

AU - Israel, Elliot

AU - Drazen, Jeffrey M.

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N2 - Background: Eotaxin, a CC chemokine expressed in the asthmatic lung, has been associated with impaired lung function. The role of its variant form is unknown. Objective: The purpose of this study was to detect the population frequency and effects of a known single-nucleotide polymorphism in the eotaxin gene in which a threonine residue (THR23) is substituted for the wild-type alanine (ALA23) at the 23rd amino acid at the terminus of the peptide leader sequence. Methods: We measured eotaxin protein secretion in 293 cells transfected with expression vectors and in PBMCs obtained from individuals bearing the alternative forms of the gene. A case-control study of plasma eotaxin levels and eosinophil counts, a comparison of baseline lung function by genotype in a population of 806 subjects with asthma, and a comparison of the allele frequency with a nonasthmatic population were performed. Results: Human 293 cells and PBMCs with THR23 variant eotaxin secreted significantly less eotaxin protein than did ALA23-bearing cells. In the case-control study, THR23-THR23 individuals had lower plasma levels of eotaxin (310[240-350] vs 420 [270-700] pg/mL; P < .05) and eosinophil counts (120[5-220] vs 190 [110-470] cells/μL; P < .05) than ALA23-ALA23 subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR23 eotaxin (percent of predicted FEV1 65% ± 3.5% [THR23-THR23] vs 58% ± 0.9% [THR23-ALA23] and 56% ± 0.5% [ALA23-ALA23]; P < .05). Conclusion: The THR23 variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma.

AB - Background: Eotaxin, a CC chemokine expressed in the asthmatic lung, has been associated with impaired lung function. The role of its variant form is unknown. Objective: The purpose of this study was to detect the population frequency and effects of a known single-nucleotide polymorphism in the eotaxin gene in which a threonine residue (THR23) is substituted for the wild-type alanine (ALA23) at the 23rd amino acid at the terminus of the peptide leader sequence. Methods: We measured eotaxin protein secretion in 293 cells transfected with expression vectors and in PBMCs obtained from individuals bearing the alternative forms of the gene. A case-control study of plasma eotaxin levels and eosinophil counts, a comparison of baseline lung function by genotype in a population of 806 subjects with asthma, and a comparison of the allele frequency with a nonasthmatic population were performed. Results: Human 293 cells and PBMCs with THR23 variant eotaxin secreted significantly less eotaxin protein than did ALA23-bearing cells. In the case-control study, THR23-THR23 individuals had lower plasma levels of eotaxin (310[240-350] vs 420 [270-700] pg/mL; P < .05) and eosinophil counts (120[5-220] vs 190 [110-470] cells/μL; P < .05) than ALA23-ALA23 subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR23 eotaxin (percent of predicted FEV1 65% ± 3.5% [THR23-THR23] vs 58% ± 0.9% [THR23-ALA23] and 56% ± 0.5% [ALA23-ALA23]; P < .05). Conclusion: The THR23 variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma.

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KW - Single-nucleotide polymorphism

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