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Association analysis of N-acetyl transferase-2 polymorphisms with aspirin intolerance among asthmatics.

Authors
Kim, JM; Park, BL; Park, SM; Lee, SH; Kim, MO; Jung, S; Lee, EH; Uh, ST; Park, JS; Choi, JS; Kim, YH; Kim, MK; Choi, IS; Cho, SH; Choi, BW; Park, HS; Chang, HS; Shin, HD; Park, CS
Citation
Pharmacogenomics, 11(7):951-958, 2010
Journal Title
Pharmacogenomics
ISSN
1462-24161744-8042
Abstract
AIMS: 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. MATERIALS & 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). CONCLUSION: 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.
MeSH terms
AdultAllelesArylamine N-Acetyltransferase/*geneticsAsian Continental Ancestry Group/geneticsAspirin/*adverse effects/immunologyAsthma/*genetics/physiopathologyCase-Control StudiesCysteine/immunologyDrug Hypersensitivity/*geneticsDrug Tolerance/geneticsFemaleGene FrequencyGenotypeHaplotypesHumansKoreaLeukotrienes/immunologyMaleMiddle Aged*Polymorphism, GeneticPolymorphism, Single Nucleotide
DOI
10.2217/pgs.10.65
PMID
20602614
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Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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