BACKGROUND: It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported. METHODS: Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5). RESULTS: Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment. CONCLUSIONS: It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients. The genetic study could identify those patients most likely to respond to montelukast.
BACKGROUND: It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported. METHODS: Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5). RESULTS: Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment. CONCLUSIONS: It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthmapatients. The genetic study could identify those patients most likely to respond to montelukast.
Authors: E B Mougey; C Chen; K G Tantisira; K V Blake; S P Peters; R A Wise; S T Weiss; J J Lima Journal: Pharmacogenomics J Date: 2012-02-28 Impact factor: 3.550
Authors: Jason E Lang; Edward B Mougey; Md Jobayer Hossain; Floyd Livingston; P Babu Balagopal; Scott Langdon; John J Lima Journal: Ann Am Thorac Soc Date: 2019-05
Authors: George D Leikauf; Vincent J Concel; Kiflai Bein; Pengyuan Liu; Annerose Berndt; Timothy M Martin; Koustav Ganguly; An Soo Jang; Kelly A Brant; Richard A Dopico; Swapna Upadhyay; Clinton Cario; Y P Peter Di; Louis J Vuga; Emrah Kostem; Eleazar Eskin; Ming You; Naftali Kaminski; Daniel R Prows; Daren L Knoell; James P Fabisiak Journal: Am J Respir Cell Mol Biol Date: 2013-09 Impact factor: 6.914