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J Allergy Clin Immunol. 2001 Dec;108(6):946-53.

Variant eotaxin: its effects on the asthma phenotype.

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1
Combined Program in Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

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 (THR(23)) is substituted for the wild-type alanine (ALA(23)) 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 THR(23) variant eotaxin secreted significantly less eotaxin protein than did ALA(23)-bearing cells. In the case-control study, THR(23)-THR(23) 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/microL; P < .05) than ALA(23)-ALA(23) subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR(23) eotaxin (percent of predicted FEV(1), 65% +/- 3.5% [THR(23)-THR(23)] vs 58% +/- 0.9% [THR(23)-ALA(23)] and 56% +/- 0.5% [ALA(23)-ALA(23)]; P < .05).

CONCLUSION:

The THR(23) variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma.

PMID:
11742272
DOI:
10.1067/mai.2001.120135
[Indexed for MEDLINE]
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