Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma

H. Kotani, R. Kishi, A. Mouri, T. Sashio, J. Shindo, A. Shiraki, T. Hiramatsu, S. Iwata, H. Taniguchi, O. Nishiyama, M. Iwata, R. Suzuki, H. Gonda, T. Niwa, M. Kondo, Y. Hasegawa, H. Kume, Y. Noda

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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 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 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 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.

Original languageEnglish
Pages (from-to)112-116
Number of pages5
JournalJournal of Clinical Pharmacy and Therapeutics
Volume37
Issue number1
DOIs
Publication statusPublished - 01-02-2012

Fingerprint

montelukast
Leukotrienes
Asthma
Single Nucleotide Polymorphism
Genotype
Genes
Leukotriene Antagonists
Forced Expiratory Volume
Sample Size
Alleles

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Kotani, H. ; Kishi, R. ; Mouri, A. ; Sashio, T. ; Shindo, J. ; Shiraki, A. ; Hiramatsu, T. ; Iwata, S. ; Taniguchi, H. ; Nishiyama, O. ; Iwata, M. ; Suzuki, R. ; Gonda, H. ; Niwa, T. ; Kondo, M. ; Hasegawa, Y. ; Kume, H. ; Noda, Y. / Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma. In: Journal of Clinical Pharmacy and Therapeutics. 2012 ; Vol. 37, No. 1. pp. 112-116.
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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 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 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 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.",
author = "H. Kotani and R. Kishi and A. Mouri and T. Sashio and J. Shindo and A. Shiraki and T. Hiramatsu and S. Iwata and H. Taniguchi and O. Nishiyama and M. Iwata and R. Suzuki and H. Gonda and T. Niwa and M. Kondo and Y. Hasegawa and H. Kume and Y. Noda",
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Kotani, H, Kishi, R, Mouri, A, Sashio, T, Shindo, J, Shiraki, A, Hiramatsu, T, Iwata, S, Taniguchi, H, Nishiyama, O, Iwata, M, Suzuki, R, Gonda, H, Niwa, T, Kondo, M, Hasegawa, Y, Kume, H & Noda, Y 2012, 'Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma', Journal of Clinical Pharmacy and Therapeutics, vol. 37, no. 1, pp. 112-116. https://doi.org/10.1111/j.1365-2710.2011.01248.x

Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma. / Kotani, H.; Kishi, R.; Mouri, A.; Sashio, T.; Shindo, J.; Shiraki, A.; Hiramatsu, T.; Iwata, S.; Taniguchi, H.; Nishiyama, O.; Iwata, M.; Suzuki, R.; Gonda, H.; Niwa, T.; Kondo, M.; Hasegawa, Y.; Kume, H.; Noda, Y.

In: Journal of Clinical Pharmacy and Therapeutics, Vol. 37, No. 1, 01.02.2012, p. 112-116.

Research output: Contribution to journalArticle

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T1 - Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma

AU - Kotani, H.

AU - Kishi, R.

AU - Mouri, A.

AU - Sashio, T.

AU - Shindo, J.

AU - Shiraki, A.

AU - Hiramatsu, T.

AU - Iwata, S.

AU - Taniguchi, H.

AU - Nishiyama, O.

AU - Iwata, M.

AU - Suzuki, R.

AU - Gonda, H.

AU - Niwa, T.

AU - Kondo, M.

AU - Hasegawa, Y.

AU - Kume, H.

AU - Noda, Y.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - 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 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 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 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.

AB - 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 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 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 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.

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