Adenosine deaminase and adenosine receptor polymorphisms in aspirin-intolerant asthma.
In asthmatic airways, adenosine is a potent bronchoconstrictor with either pro- or anti-inflammatory effects depending on receptor interactions. While aspirin has been suggested to mediate adenosine action, the roles of adenosine and its receptors in aspirin-intolerant asthma (AIA) are not well-defined. Therefore, we evaluated associations between genetic polymorphisms of adenosine deaminase and the four adenosine receptors (A(1), A(2A), A(2B), and A(3)) with the AIA phenotype. The genes for adenosine deaminase (ADA) and the four adenosine receptors (ADORA1, ADORA2A, ADORA2B, and ADORA3) were screened by direct sequencing, and 13 single nucleotide polymorphisms (SNPs) were selected among 23 polymorphisms. Using multivariate logistic regression analysis, we compared the frequencies of SNP genotypes and haplotypes among 136 patients with AIA, 181 patients with aspirin-tolerant asthma (ATA), and 183 normal individuals. We found significant differences between normal and patients with AIA in the ADORA1 SNP genotype frequencies for 1405C>T (P=0.001) and A102A (P=0.013). No other significant associations were detected for the other SNPs. In the haplotype analysis, ht[C-T-G] (P=0.003) and ht[A-C-G] (P=0.032) in ADORA1 and ht[A-T] in ADORA2 (P=0.013) were significantly associated with AIA. Genetic polymorphisms of adenosine receptors A(1) and A(2A) were associated with AIA, suggesting that adenosine might play a crucial role in the development of AIA through interactions with the A(1) and A(2A) receptors.
Kim
Sang-Heon
SH
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.
Kim
Yoon-Keun
YK
Park
Heung-Woo
HW
Kim
Sang-Hoon
SH
Kim
Seung-Hyun
SH
Ye
Young-Min
YM
Min
Kyung-Up
KU
Park
Hae-Sim
HS
D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D001241:Aspirin; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D004342:Drug Hypersensitivity / Q000235:genetics*; D004361:Drug Tolerance; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043682:Receptor, Adenosine A1 / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000235:genetics; D043704:Receptor, Adenosine A2B / Q000235:genetics; D043684:Receptor, Adenosine A3 / Q000235:genetics; D018047:Receptors, Purinergic P1 / Q000235:genetics*
D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D000243:Adenosine Deaminase; D001241:Aspirin