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
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Variant eotaxin: Its effects on the asthma phenotype'. Together they form a unique fingerprint.

  • Cite this

    Nakamura, H., Luster, A. D., Nakamura, T., In, K. H., Sonna, L. A., Deykin, A., Israel, E., Drazen, J. M., & 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