ALOX5 promoter genotype, asthma severity and LTC production by eosinophils.
Allergy
; 61(1): 97-103, 2006 Jan.
Article
em En
| MEDLINE
| ID: mdl-16364163
ABSTRACT
BACKGROUND:
The number of Sp1-Egr1 binding tandem repeats at the ALOX5 promoter influences gene transcription and may modify the response to anti-leukotriene treatment. The relationship of ALOX5 variants to asthma severity and leukotriene production by eosinophils is unknown.OBJECTIVE:
To characterize ALOX5 mRNA expression and cysteinyl-leukotriene production by eosinophils from individuals bearing ALOX5 promoter deletional variants and their association with the severity of childhood asthma.METHODS:
Eosinophils from adult asthmatics bearing only variant alleles (with other than five tandem repeats on both chromosomes, non5/non5) or no variant alleles (5/5) were cultured in vitro and ALOX5 expression and leukotriene secretion were measured. A total of 621 children with mild or moderate-severe asthma were genotyped at the ALOX5 core promoter.RESULTS:
Asthmatics with non5/non5 genotype expressed less ALOX5 mRNA and produced less LTC4 into culture supernatants than 5/5 individuals (6.4 +/- 2.0 and 20.0 +/- 5.0 pg/ml, n = 5; P < 0.05). More asthmatic children bearing non5/non5 genotype had moderate-severe asthma than children with the 5/5 genotype (5.3% vs. 1.4%, P = 0.008). Multivariate logistic regression identified ALOX5 promoter genotype as a significant predictor of disease severity (OR = 3.647, 95% CI 1.146-11.608, P = 0.03). Consistent with these findings, children bearing the non5/non5 genotype had greater bronchomotor response to exercise as measured by the maximum fall after exercise and the area under the exercise curve (P < 0.05 for both).CONCLUSION:
Our results suggest that children who express the asthma phenotype despite having a genetic variant that impairs their ability to express ALOX5 have more severe disease and thus are more likely to have asthma symptoms.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Araquidonato 5-Lipoxigenase
/
Regiões Promotoras Genéticas
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Leucotrieno C4
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Allergy
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Turquia