ALOX5 promoter genotype and response to montelukast in moderate persistent asthma.
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.
Telleria
Juan J
JJ
Institute of Biology and Molecular Genetics (IBGM/CSIC), University of Valladolid, Valladolid, Spain. juangose.telleria@uva.es <juangose.telleria@uva.es>
Blanco-Quiros
Alfredo
A
Varillas
David
D
Armentia
Alicia
A
Fernandez-Carvajal
Isabel
I
Jesus Alonso
M
M
Diez
Ignacio
I
D000085:Acetates / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D003521:Cyclopropanes; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011804:Quinolines / Q000627:therapeutic use*; D017678:Sex Distribution; D013440:Sulfides; D020080:Tandem Repeat Sequences / Q000235:genetics; D016896:Treatment Outcome
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D007073:Immunoglobulin E; D001094:Arachidonate 5-Lipoxygenase; C093875:montelukast