Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma
| Autor: | Masashi Kondo, R. Suzuki, Toyokazu Sashio, M. Iwata, Yoshinori Hasegawa, Tetsuo Hiramatsu, H. Gonda, Yukihiro Noda, H. Taniguchi, Hisashi Kotani, Hiroaki Kume, Akihiro Mouri, Joe Shindo, Rina Kishi, Susumu Iwata, Anna Shiraki, Osamu Nishiyama, T. Niwa |
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| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Leukotriene education.field_of_study business.industry Population Single-nucleotide polymorphism medicine.disease respiratory tract diseases Genotype frequency Cysteinyl leukotriene receptor 1 immune system diseases Immunology Medicine Pharmacology (medical) business education Pharmacogenetics Montelukast medicine.drug Asthma |
| Zdroj: | Journal of Clinical Pharmacy and Therapeutics. 37:112-116 |
| ISSN: | 0269-4727 |
| Popis: | Summary 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 (FEV1·0) and patients’ subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. Results and Discussion: 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 FEV1·0. The PEF and FEV1·0 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 and Conclusion: 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. |
| Databáze: | OpenAIRE |
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