CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients.
OBJECTIVE
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 (> or = 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).


CONCLUSIONS
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.
Kim
Seung-Hyun
SH
Ajou University School of Medicine, Department of Allergy and Rheumatology, Yeongtonggu Wonchondong San-5, Suwon 443-721, Korea.
Ye
Young-Min
YM
Hur
Gyu Young
GY
Lee
Soo-Keol
SK
Sampson
Anthony P
AP
Lee
Hyun-Young
HY
Park
Hae-Sim
HS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy; D002648:Child; D004342:Drug Hypersensitivity / Q000235:genetics*; D005541:Forced Expiratory Volume; D006801:Humans; D007723:Korea; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018077:Receptors, Leukotriene / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor; D001241:Aspirin