RT Journal Article
SR Electronic
T1 Cyclooxygenase-1 gene polymorphisms in patients with different asthma phenotypes and atopy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 249
OP 256
DO 10.1183/09031936.05.00140104
VO 26
IS 2
A1 J. Shi
A1 N. L. A. Misso
A1 D. L. Duffy
A1 B. Bradley
A1 R. Beard
A1 P. J. Thompson
A1 M-A. Kedda
YR 2005
UL http://erj.ersjournals.com/content/26/2/249.abstract
AB Cyclooxygenase-1 (COX-1) regulates the biosynthesis of prostaglandins, which are important mediators in asthma. The possible association of COX-1 gene polymorphisms with asthma has not been investigated. The allele frequencies of 20 COX-1 polymorphisms were determined in a random Australian Caucasian population using MassARRAY technology. Informative and potentially functional promoter (c.8592C>T, c.1676C>T) and coding region (c.22C>T, c.50C>T) polymorphisms were investigated in carefully phenotyped patients with mild (n = 316), moderate (n = 241), severe (n = 86) or aspirin-intolerant asthma (AIA) (n = 58), and in nonasthmatic subjects (n = 477). There were no allelic, genotypic or haplotypic associations between these four polymorphisms and asthma or asthma severity. Over-representation of the c.50TT genotype among AIA patients (3.4%) compared with aspirin-tolerant patients (0.8%), and a global haplotype association with AIA did not reach statistical significance. The c.22TT genotype was less frequent among atopic (0.1%) rather than nonatopic individuals (1.2%; odds ratio = 9.05, 95% confidence interval 1.01–81.29). In conclusion, the present investigation of cyclooxygenase-1 polymorphisms in asthma indicates that they do not appear to play a substantial role in genetic pre-disposition for asthma or asthma severity. However, the c.22TT genotype confers a small protective effect against atopy. Potential associations with aspirin-intolerant asthma were identified and warrant further investigation in a larger population of aspirin-intolerant asthma patients.