Drs. Lang and Mougey contributed equally to the manuscript. A complete listing of the American Lung Association Asthma Clinical Research Centers (ALA-ACRCs) can be found as an Appendix S1.
ALOX5 Polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma
Article first published online: 22 APR 2013
© 2012 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 43, Issue 5, pages 512–520, May 2013
How to Cite
Clinical & Experimental Allergy, 2013 (43)512–520., , , , , , ,
- Issue published online: 22 APR 2013
- Article first published online: 22 APR 2013
- Accepted manuscript online: 22 DEC 2012 04:38AM EST
- Manuscript Accepted: 14 DEC 2012
- Manuscript Revised: 6 NOV 2012
- Manuscript Received: 21 AUG 2012
- asthma control;
- exhaled nitric oxide;
- genetic association;
Identification of risk factors for reduced asthma control could improve the understanding and treatment of asthma. A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy, but its impact on disease control remains unclear.
We sought to determine if the ALOX5 promoter SP1 tandem repeat polymorphism was associated with changes in cysteinyl leukotriene production, lung function, airway inflammation and asthma control score.
We analysed 270 children, 6- to 17-years old, with poorly controlled asthma enrolled in a 6-month clinical trial (NCT00604851). In secondary analysis, we associated the ALOX5 promoter SP1 tandem repeat polymorphism genotype (rs59439148) with asthma outcomes using both additive and recessive genetic models. We evaluated FEV1 percent predicted, symptom control, exhaled nitric oxide and urinary LTE4 levels.
Of all children, 14.8% (40/270) (and 28% (38/135) of African Americans) carried two non-5-repeat variant alleles of rs59439148. Children who were homozygous for variant alleles had significantly higher urinary LTE4 levels (38 vs. 30 nmol/mol creatinine, P = 0.0134), significantly worse FEV1% predicted (84 vs. 91, P = 0.017) and a trend towards worse asthma control. FEV1% predicted values were significantly negatively correlated with urinary LTE4 (r = −0.192, P = 0.009).
Conclusion and Clinical Relevance
Carrying two copies of a minor variant ALOX5 promoter SP1 tandem repeat allele contributes to increased cysLT exposure as determined by urinary LTE4 levels, reduced lung function and potentially worse asthma control. ALOX5 promoter SP1 tandem repeat genotype may be a risk factor for worse asthma outcomes.