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CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients

CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients
CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients
Objectives: Leukotriene receptor antagonists (LTRA), such as montelukast, have been used as a first-line treatment for patients with aspirin-intolerant asthma (AIA). This study evaluated associations between the clinical requirement for LTRA and genetic polymorphisms of the ALOX5, LTC4S, COX-2, CysLTR1 and TBXA2R genes in the arachidonic acid cascade in the long-term management of 89 AIA patients from a Korean population.
Methods: Asthma control status was monitored for 1 year with maintenance medications of inhaled corticosteroid and oral LTRA, and AIA patients were classified into three groups according to the mean montelukast dose required per month to maintain asthma control for 1 year: group I (?200 mg montelukast/month; n = 37), group II (5–150 mg/month; n = 25) and group III (<5 mg/month; n = 27). Genetic polymorphisms in the arachidonic acid cascade were determined using a single-base extension method.
Results: We found that there was a significant difference in the genotype frequency of the CysLTR1 promoter polymorphism -634C > T among the three groups (p = 0.007 for group I vs group II, p = 0.017 for group I vs group III), while there were no significant associations between LTRA requirements and polymorphisms of the other genes. The patients with the variant genotype (CT or TT) of the -634C = T CysLTR1 promoter polymorphism showed a higher expression level than those with the common genotype (CC).
Conclusion: These findings indicate that the CysLTR1 promoter polymorphism is a useful genetic marker for predicting LTRA requirements in the long-term management of AIA patients.
1143-1150
Kim, S.H.
1e5e8a15-6524-419a-b2f9-73e9653de401
Ye, Y.M.
173a9d18-0493-4e4a-a08d-cac83cc9711f
Hur, G.Y.
3bf49a50-fb25-4a81-b141-07410cd6a6d0
Lee, S.K.
2bda7741-8d13-42f7-937a-a865fe2df798
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Lee, H.Y.
43b45c39-d1f0-4778-a049-883b907bf48d
Park, H.S.
37395c90-bc75-4c48-9d46-daac0107844b
Kim, S.H.
1e5e8a15-6524-419a-b2f9-73e9653de401
Ye, Y.M.
173a9d18-0493-4e4a-a08d-cac83cc9711f
Hur, G.Y.
3bf49a50-fb25-4a81-b141-07410cd6a6d0
Lee, S.K.
2bda7741-8d13-42f7-937a-a865fe2df798
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Lee, H.Y.
43b45c39-d1f0-4778-a049-883b907bf48d
Park, H.S.
37395c90-bc75-4c48-9d46-daac0107844b

Kim, S.H., Ye, Y.M., Hur, G.Y., Lee, S.K., Sampson, A.P., Lee, H.Y. and Park, H.S. (2007) CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients. Pharmacogenomics, 8 (9), 1143-1150. (doi:10.2217/14622416.8.9.1143).

Record type: Article

Abstract

Objectives: Leukotriene receptor antagonists (LTRA), such as montelukast, have been used as a first-line treatment for patients with aspirin-intolerant asthma (AIA). This study evaluated associations between the clinical requirement for LTRA and genetic polymorphisms of the ALOX5, LTC4S, COX-2, CysLTR1 and TBXA2R genes in the arachidonic acid cascade in the long-term management of 89 AIA patients from a Korean population.
Methods: Asthma control status was monitored for 1 year with maintenance medications of inhaled corticosteroid and oral LTRA, and AIA patients were classified into three groups according to the mean montelukast dose required per month to maintain asthma control for 1 year: group I (?200 mg montelukast/month; n = 37), group II (5–150 mg/month; n = 25) and group III (<5 mg/month; n = 27). Genetic polymorphisms in the arachidonic acid cascade were determined using a single-base extension method.
Results: We found that there was a significant difference in the genotype frequency of the CysLTR1 promoter polymorphism -634C > T among the three groups (p = 0.007 for group I vs group II, p = 0.017 for group I vs group III), while there were no significant associations between LTRA requirements and polymorphisms of the other genes. The patients with the variant genotype (CT or TT) of the -634C = T CysLTR1 promoter polymorphism showed a higher expression level than those with the common genotype (CC).
Conclusion: These findings indicate that the CysLTR1 promoter polymorphism is a useful genetic marker for predicting LTRA requirements in the long-term management of AIA patients.

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Published date: September 2007

Identifiers

Local EPrints ID: 59353
URI: http://eprints.soton.ac.uk/id/eprint/59353
PURE UUID: 30604a84-02da-4996-bc7c-3960ad50dbb3
ORCID for A.P. Sampson: ORCID iD orcid.org/0009-0008-9653-8935

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Date deposited: 02 Sep 2008
Last modified: 16 Mar 2024 02:51

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Contributors

Author: S.H. Kim
Author: Y.M. Ye
Author: G.Y. Hur
Author: S.K. Lee
Author: A.P. Sampson ORCID iD
Author: H.Y. Lee
Author: H.S. Park

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