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Associations between CYP2E1 promoter polymorphisms and plasma 1,3-dimethyluric acid/theophylline ratios
DC Field | Value | Language |
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dc.contributor.author | Yoon, Yeomin | - |
dc.contributor.author | Park, Hyung-Doo | - |
dc.contributor.author | Park, Kyoung Un | - |
dc.contributor.author | Kim, Jin Q | - |
dc.contributor.author | Chang, Yoon-Seok | - |
dc.contributor.author | Song, Junghan | - |
dc.date.accessioned | 2009-11-13T04:16:43Z | - |
dc.date.available | 2009-11-13T04:16:43Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | Eur J Clin Pharmacol 62:627-631 | en |
dc.identifier.issn | 0031-6970 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16841220 | - |
dc.identifier.uri | https://hdl.handle.net/10371/12120 | - |
dc.description.abstract | OBJECTIVE: Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigated the associations between 1,3-DMU/theophylline ratios and genetic polymorphisms of CYP2E1 and CYP1A2. METHODS: Polymerase chain reaction (PCR) and direct sequencing or PCR-restriction fragment length polymorphism (RFLP) were performed to analyze CYP2E1 and CYP1A2 promoter polymorphisms in 62 Korean asthma patients. Plasma theophylline and 1,3-DMU levels were measured by liquid chromatography-tandem mass spectrometry. RESULTS: Eleven polymorphisms including Ins(96), -1566 T>A, -1515 T>G, -1414 C>T, -1295 G>C, -1055 C>T, -1027 T>C, -930 A>G, -807 T>C, -352 A>G, and -333 T>A were detected in the 5' flanking region of the CYP2E1 gene (numbering according to GenBank Accession number NT_017795). Of these, five single nucleotide polymorphisms (SNPs) (-1566 T>A, -1295 G>C, -1055 C>T, -1027 T>C, and -807 T>C) were closely linked. Another three polymorphisms (Ins(96,) -930 A>G, and -352 A>G) and two polymorphisms (-1515 T>G and -333 T>A) were also closely linked. The five closely linked polymorphisms were associated with significantly different 1,3-DMU/theophylline ratios between heterozygotes plus homozygotes of a rare allele (n=23, 0.0368+/-0.0171) and common allelic homozygotes (n=39, 0.0533+/-0.0343) (p=0.024 by Mann-Whitney U test). In the CYP1A2 gene, the -2964G>A polymorphisms exhibited a significant difference in 1,3-DMU/theophylline levels between heterozygotes plus homozygotes of a rare allele (n=30, 0.0406+/-0.0272) and homozygotes of a common allele (n=32, 0.0534+/-0.0316) (p=0.032). CONCLUSION: We confirm that hydroxylation at the 8 position of theophylline (1,3-DMU) is significantly affected by genetic polymorphism in CYP2E1 in addition to CYP1A2. | en |
dc.language.iso | en | - |
dc.publisher | Springer Verlag | en |
dc.subject | Alleles | en |
dc.subject | Asthma/metabolism | en |
dc.subject | Cytochrome P-450 CYP1A2/*genetics | en |
dc.subject | Cytochrome P-450 CYP2E1/*genetics | en |
dc.subject | Genotype | en |
dc.subject | Pharmacogenetics | en |
dc.subject | Polymerase Chain Reaction | en |
dc.subject | Polymorphism, Restriction Fragment Length | en |
dc.subject | Theophylline/blood/*metabolism | en |
dc.subject | Uric Acid/*analogs & derivatives/blood | en |
dc.subject | Polymorphism, Genetic | - |
dc.title | Associations between CYP2E1 promoter polymorphisms and plasma 1,3-dimethyluric acid/theophylline ratios | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 윤여민 | - |
dc.contributor.AlternativeAuthor | 박형두 | - |
dc.contributor.AlternativeAuthor | 박경운 | - |
dc.contributor.AlternativeAuthor | 김진규 | - |
dc.contributor.AlternativeAuthor | 장윤석 | - |
dc.contributor.AlternativeAuthor | 송정한 | - |
dc.identifier.doi | 10.1007/s00228-006-0165-4 | - |
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