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http://purl.uniprot.org/citations/19891553http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19891553http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.org/dc/terms/identifier"doi:10.2217/pgs.09.100"xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Kim Y.S."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Kim S.H."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Song J."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Kim Y.K."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Park H.S."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Park J.S."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Kim B.H."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Chang Y.S."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Kim S.H.'"xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Shin E.S."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Min K.U."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Jang I.J."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Jee Y.K."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Bahn J.W."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/author"Kim S.H.''"xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/name"Pharmacogenomics"xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/pages"1767-1779"xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/title"Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis."xsd:string
http://purl.uniprot.org/citations/19891553http://purl.uniprot.org/core/volume"10"xsd:string
http://purl.uniprot.org/citations/19891553http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19891553
http://purl.uniprot.org/citations/19891553http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19891553
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