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 language | English |
|---|---|
| Article number | 15482 |
| Pages (from-to) | 946-953 |
| Number of pages | 8 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 108 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2001 Jan 1 |
| Externally published | Yes |
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Keywords
- Asthma
- Chemokines
- Eotaxin
- Human genetics
- Single-nucleotide polymorphism
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Variant eotaxin
T2 - Its effects on the asthma phenotype
AU - Nakamura, Hidetoshi
AU - Luster, Andrew D.
AU - Nakamura, Toshiko
AU - In, Kwang Ho
AU - Sonna, Larry A.
AU - Deykin, Aaron
AU - Israel, Elliot
AU - Drazen, Jeffrey M.
AU - Lilly, Craig M.
PY - 2001/1/1
Y1 - 2001/1/1
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.
KW - Asthma
KW - Chemokines
KW - Eotaxin
KW - Human genetics
KW - Single-nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=0035216218&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035216218&partnerID=8YFLogxK
U2 - 10.1067/mai.2001.120135
DO - 10.1067/mai.2001.120135
M3 - Article
C2 - 11742272
AN - SCOPUS:0035216218
VL - 108
SP - 946
EP - 953
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 6
M1 - 15482
ER -