Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma.
BACKGROUND
The A to C transversion in the promoter region of the gene encoding leukotriene C4 synthase (LTC4S) is proposed to be associated with the development of aspirin-induced asthma (AIA).


OBJECTIVE
We investigated the frequency of the polymorphism in Japanese population and its association with clinical characteristics and cysteinyl leukotriene production.


METHODS
Genotyping of LTC4S gene promoter was performed on 60 patients with AIA, 100 patients with aspirin-tolerant asthma (ATA), and 110 control subjects. We assessed the basal levels of urinary LTE4, the increment of urinary LTE4 on venous aspirin challenge, and LTC4S activity in peripheral blood eosinophils.


RESULTS
The frequency of the variant C allele was significantly higher in patients with AIA (frequency of allele [q] = 0.192) than in patients with ATA (q = 0.110, P =.042). Variant C-allelic carriers experienced asthma at a significantly younger age (31.8 +/- 2.9 years [mean +/- SEM]) than wild-type A homozygotes (41.3 +/- 2.2 years, P =.007). Basal levels of LTE4 and the increment of urinary LTE4 on venous aspirin challenge did not show a difference between wild-type A homozygotes and variant C-allelic carriers. There was no relationship between the polymorphism and the LTC4S activity in eosinophils, although LTC4S activities were significantly higher in patients with AIA than in patients with ATA.


CONCLUSIONS
Our findings reveal the lack of functionality of the polymorphism in the LTC4S gene, whereas this polymorphism might have some effect on the development of AIA, probably in linkage disequilibrium with another causatively important mutation.
Kawagishi
Yukio
Y
First Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Mita
Haruhisa
H
Taniguchi
Masami
M
Maruyama
Muneharu
M
Oosaki
Rokuo
R
Higashi
Noritaka
N
Kashii
Tatsuhiko
T
Kobayashi
Masashi
M
Akiyama
Kazuo
K
D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D004342:Drug Hypersensitivity / Q000201:enzymology / Q000235:genetics*; D004804:Eosinophils / Q000201:enzymology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
D017999:Leukotriene E4; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D001241:Aspirin