Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma.
J Clin Pharm Ther
; 37(1): 112-6, 2012 Feb.
Article
in En
| MEDLINE
| ID: mdl-21385196
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability.METHODS:
To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4-8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1·0) ) and patients' subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. RESULTS ANDDISCUSSION:
Two single-nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0) . The PEF and FEV(1·0) responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17). WHAT IS NEW ANDCONCLUSION:
Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Asthma
/
Arachidonate 5-Lipoxygenase
/
Anti-Asthmatic Agents
/
Epoxide Hydrolases
/
Acetates
Type of study:
Clinical_trials
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
J Clin Pharm Ther
Journal subject:
FARMACIA
/
TERAPEUTICA
Year:
2012
Document type:
Article
Affiliation country:
Japón