期刊
CLINICAL AND EXPERIMENTAL ALLERGY
卷 43, 期 5, 页码 512-520出版社
WILEY
DOI: 10.1111/cea.12076
关键词
5-Lipoxygenase; ALOX5; asthma; asthma control; children; exhaled nitric oxide; FEV1; genetic association; leukotriene
资金
- James and Esther King Biomedical Research Program/Florida Department of Health [9KN06]
- National Heart Lung and Blood Institute [U01HL080433, 1K23HL096838]
- American Lung Association
- Takeda Pharmaceuticals North America, Inc
- GlaxoSmithKline
Background 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. Objective 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. Methods 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. Results 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. 30nmol/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.
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