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Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis.
DC Field | Value | Language |
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dc.contributor.author | Kim, SH | - |
dc.contributor.author | Bahn, JW | - |
dc.contributor.author | Kim, YK | - |
dc.contributor.author | Chang, YS | - |
dc.contributor.author | Shin, ES | - |
dc.contributor.author | Kim, YS | - |
dc.contributor.author | Park, JS | - |
dc.contributor.author | Kim, BH | - |
dc.contributor.author | Jang, IJ | - |
dc.contributor.author | Song, J | - |
dc.contributor.author | Park, HS | - |
dc.contributor.author | Min, KU | - |
dc.contributor.author | Jee, YK | - |
dc.date.accessioned | 2010-12-01T02:42:21Z | - |
dc.date.available | 2010-12-01T02:42:21Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 1462-2416 | - |
dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/367 | - |
dc.description.abstract | AIMS: Although some genetic risk factors have been reported for the development of hepatitis due to anti-TB drugs, an extensive candidate gene approach evaluating drug-metabolizing enzymes has not been attempted. This study aimed to investigate the association of genetic polymorphisms in drug-metabolizing enzymes with anti-TB drug-induced hepatitis.
MATERIALS & METHODS: We compared genotype distributions of tagging SNPs in promoter, exons and haplotypes in seven drug-metabolizing enzyme genes (CYP2C9, CYP2C19, CYP2D6, CYP2E1, NAT2, UGT1A1 and UGT1A3) between 67 cases and 159 controls. RESULTS: Among four tagging SNPs of N-acetyltransferase 2 (NAT2), -9796T>A in promoter and R197Q were significantly associated (p = 0.0016 and p = 0.0007, respectively). NAT2 haplotype 2 [A-A-A-G] carrying A allele of -9796T>A and A allele of R197Q showed significant association (p = 0.0004). However, there was no significant association between genotypes of other enzyme-metabolizing genes and anti-TB drug-induced hepatitis. The constructs containing -9796A of NAT2 showed significantly lower luciferase activity (p < 0.01), suggesting decreased expression of NAT2. The variant alleles and haplotype 2 showed significantly higher peak serum levels of isoniazid, lower acetyl isoniazid:isoniazid ratio and lower isoniazid clearance compared with wild-types. CONCLUSION: These findings suggest that genetic variants in the promoter and exons of NAT2 increase the risk of anti-TB drug-induced hepatitis by modifying acetylation phenotypes and/or gene expression of NAT2, and there is no essential role for genetic mutation of the other metabolizing enzymes in the development of this adverse reaction. | - |
dc.language.iso | en | - |
dc.subject.MESH | Acetylation | - |
dc.subject.MESH | Antitubercular Agents | - |
dc.subject.MESH | Arylamine N-Acetyltransferase | - |
dc.subject.MESH | Drug-Induced Liver Injury | - |
dc.subject.MESH | Haplotypes | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Isoniazid | - |
dc.subject.MESH | Polymorphism, Single Nucleotide | - |
dc.title | Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis. | - |
dc.type | Article | - |
dc.identifier.pmid | 19891553 | - |
dc.identifier.url | http://www.futuremedicine.com/doi/abs/10.2217/pgs.09.100?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed | - |
dc.contributor.affiliatedAuthor | 김, 승현 | - |
dc.contributor.affiliatedAuthor | 박, 해심 | - |
dc.type.local | Journal Papers | - |
dc.identifier.doi | 10.2217/pgs.09.100 | - |
dc.citation.title | Pharmacogenomics | - |
dc.citation.volume | 10 | - |
dc.citation.number | 11 | - |
dc.citation.date | 2009 | - |
dc.citation.startPage | 1767 | - |
dc.citation.endPage | 1779 | - |
dc.identifier.bibliographicCitation | Pharmacogenomics, 10(11). : 1767-1779, 2009 | - |
dc.identifier.eissn | 1744-8042 | - |
dc.relation.journalid | J014622416 | - |
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