Variant eotaxin: Its effects on the asthma phenotype

초록

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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