title: Association analysis of N-acetyl transferase-2 polymorphisms with aspirin intolerance among asthmatics.
abstract: 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.
authors.affiliation: Genome Research Center for Allergy & Respiratory Disease, Soonchunhyang University Bucheon Hospital, 1174 Jung-dong, Wonmi-gu, Bucheon, Gyeonggi-do 420-767, Republic of Korea.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Kim
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Se-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Shin-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Myung-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Seok
authors.initials: S
authors.lastname: Jung
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Choi
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: 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
chemical_list: D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D003545:Cysteine; D001241:Aspirin