Association Analysis of
            <i>N</i>
            -Acetyl Transferase-2 Polymorphisms with Aspirin Intolerance Among Asthmatics

Kim, Jin Moo; Park, Byung Lae; Park, Se Min; Lee, Shin Hwa; Kim, Myung ok; Jung, Seok Won; Lee, Eun Hee; Uh, Soo Taek; Park, Jong Suk; Choi, Jae Sung; Kim, Yong Hoon; Kim, Mi Kyeong; Choi, Inseon S.; Cho, Sang Heon; Choi, Byoung Whui; Park, Hae‐Sim; Chang, Hun Soo; Shin, Hyoung Doo; Park, Choon-Sik

doi:10.2217/pgs.10.65

Cited by 22 publications

(12 citation statements)

References 38 publications

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“…In NSAID-exacerbated respiratory diseases, some links to interleukin-4 promoter polymorphisms and N-acetyl transferase-2 polymorphisms have been described in Korean patients [48,49]. …”

Section: Three Distinct Mechanisms Leading To Dhrmentioning

confidence: 99%

Classification of Drug Hypersensitivity into Allergic, p-i, and Pseudo-Allergic Forms

Pichler

Hausmann²

2016

Int Arch Allergy Immunol

130

125

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Drug hypersensitivity reactions (DHR) are clinically and functionally heterogeneous. Different subclassifications based on timing of symptom appearance or type of immune mechanism have been proposed. Here, we show that the mode of action of drugs leading to immune/inflammatory cell stimulation is a further decisive factor in understanding and managing DHR. Three mechanisms can be delineated: (a) some drugs have or gain the ability to bind covalently to proteins, form new antigens, and thus elicit immune reactions to hapten-carrier complexes (allergic/immune reaction); (b) a substantial part of immune-mediated DHR is due to a typical off-target activity of drugs on immune receptors like HLA and TCR (pharmacological interaction with immune receptors, p-i reactions); such p-i reactions are linked to severe DHR; and (c) symptoms of DHR can also appear if the drug stimulates or inhibits receptors or enzymes of inflammatory cells (pseudo-allergy). These three distinct ways of stimulations of immune or inflammatory cells differ substantially in clinical manifestations, time of appearance, dose dependence, predictability, and cross-reactivity, and thus need to be differentiated.

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“…In NSAID-exacerbated respiratory diseases, some links to interleukin-4 promoter polymorphisms and N-acetyl transferase-2 polymorphisms have been described in Korean patients [48,49]. …”

Section: Three Distinct Mechanisms Leading To Dhrmentioning

confidence: 99%

Classification of Drug Hypersensitivity into Allergic, p-i, and Pseudo-Allergic Forms

Pichler

Hausmann²

2016

Int Arch Allergy Immunol

130

125

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“…Among our significant SNPs, only the NAT2 rs4271002 has been previously investigated and found to be associated with risk of non-occupational asthma phenotypes 38, 39 . The NAT2 rs4271002 SNP was associated with an increased risk of asthma associated with paracetamol treatment in infancy 38 .…”

Section: Discussionmentioning

confidence: 99%

“…The NAT2 rs4271002 SNP was associated with an increased risk of asthma associated with paracetamol treatment in infancy 38 . Kim et al found that the NAT2 rs4271002 SNP and a haplotype carrying this variant were significantly associated with aspirin exacerbated asthma (ORs 1.61 and 1.62, respectively) 39 . They reported a putative binding site in DNA sequence for candidate transcription factor, upstream stimulatory factor (USF)-1.…”

Section: Discussionmentioning

confidence: 99%

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma

Yücesoy

Kissling

Johnson³

et al. 2015

Journal of Occupational &Amp; Environmental Medicine

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Objective To investigate whether genetic variants of N-acetyl transferase genes (NAT1 and NAT2) are associated with diisocyanate asthma (DA). Methods The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed on genomic DNA, using a 5′ nuclease PCR assay. Results The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in univariate analysis. In the first logistic regression model comparing DA+ and AW groups, the genotype combination, NAT2 rs2410556 and NAT2 rs4271002, showed association with DA risk (p=0.005). In the second model comparing DA+ and DA− groups, NAT2 rs4271002 and NAT2 rs13277605 variants were significantly associated with an increased risk of DA (p=0.002 and p=0.027, respectively). In the third model comparing DA− and AW groups, the NAT1 rs4921580 SNP and the combined genotype NAT2 rs2410556/rs4271002 showed association with the DA− phenotype (p=0.017, p<0.001, respectively). Conclusion These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.

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“…One of these, designated as rs1695, causes a missense mutation Ile105Val in the glutathione S-transferase P1 (GSTP1) enzyme. The other variant, rs4271002, is an upstream variant of the NAT2 gene, which seems to affect gene transcription and that has been previously related to aspirin-intolerant asthma [57]. Independent studies [58][59][60][61][62][63] show that NAT2 polymorphisms are related to drug hypersensitivity not only to paracetamol, but also to other drugs.…”

Section: Recent Advances In Genetic and Metabolic Biomarkers Of Hypermentioning

confidence: 99%

Drug metabolism and hypersensitivity reactions to drugs

Agúndez

Mayorga²,

García‐Martín³

2015

Current Opinion in Allergy &Amp; Clinical Immunology

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Association Analysis of N -Acetyl Transferase-2 Polymorphisms with Aspirin Intolerance Among Asthmatics

Abstract: 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.

Cited by 22 publications

References 38 publications

Classification of Drug Hypersensitivity into Allergic, p-i, and Pseudo-Allergic Forms

Classification of Drug Hypersensitivity into Allergic, p-i, and Pseudo-Allergic Forms

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma

Drug metabolism and hypersensitivity reactions to drugs

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