Association analysis of N-acetyl transferase-2 polymorphisms with aspirin intolerance among asthmatics.
OBJECTIVE
Cysteinyl leukotrienes are inactivated by acetyl coenzyme A-dependent N-acetyltransferase (NAT). Thus, functional alterations of the NAT gene may contribute to the risk of aspirin-intolerant asthma.


METHODS
Asthmatics (n = 438) were categorized into aspirin-intolerant asthma (15% or greater decrease in the forced expiratory volume in 1 s or cutaneous reactions, n = 170) or aspirin-tolerant asthma (n = 268) groups. In total, 14 polymorphisms of the NAT2 gene were genotyped by a single-base extension method.


RESULTS
The distributions of all loci of the 14 SNPs were in Hardy-Weinberg equilibrium (p > 0.05). Among the 14 SNPs, six common SNPs (minor allele frequency >5%) in a Korean population were used for haplotype construction and further statistical analysis. The logistic regression analysis demonstrated that NAT2 -9246G>C and haplotype 2 (TCACGG) were significantly associated with the risk of aspirin-intolerant asthma. The rare allele frequencies of the SNP and Ht2 were significantly higher in the aspirin-intolerant asthma group than in the aspirin-tolerant asthma group (p(corr) = 0.03 and p(corr) = 0.02 in codominant model).


CONCLUSIONS
In a large genetic epidemiology study of aspirin-intolerant asthma in a Korean population, genetic polymorphisms of NAT2 were found to be related to a risk of aspirin hypersensitivity among asthmatics.
Kim
Jin-Moo
JM
Genome Research Center for Allergy & Respiratory Disease, Soonchunhyang University Bucheon Hospital, 1174 Jung-dong, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea.
Park
Byung-Lae
BL
Park
Se-Min
SM
Lee
Shin-Hwa
SH
Kim
Myung-Ok
MO
Jung
Seok
S
Lee
Eun Hee
EH
Uh
Soo-Taek
ST
Park
Jong Sook
JS
Choi
Jae-Sung
JS
Kim
Yong-Hoon
YH
Kim
Mi-Kyeong
MK
Choi
Inseon S
IS
Cho
Sang Heon
SH
Choi
Byoung Whui
BW
Park
Hae-Sim
HS
Chang
Hun Soo
HS
Shin
Hyoung Doo
HD
Park
Choon-Sik
CS
D000328:Adult; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000009:adverse effects* / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D003545:Cysteine / Q000276:immunology; D004342:Drug Hypersensitivity / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007723:Korea; D015289:Leukotrienes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D003545:Cysteine; D001241:Aspirin