Abstract | OBJECTIVE: 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.
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Authors | Yeomin Yoon, Hyung-Doo Park, Kyoung Un Park, Jin Q Kim, Yoon-Seok Chang, Junghan Song |
Journal | European journal of clinical pharmacology
(Eur J Clin Pharmacol)
Vol. 62
Issue 8
Pg. 627-31
(Aug 2006)
ISSN: 0031-6970 [Print] Germany |
PMID | 16841220
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Uric Acid
- Theophylline
- 1,3-dimethyluric acid
- Cytochrome P-450 CYP2E1
- Cytochrome P-450 CYP1A2
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Topics |
- Alleles
- Asthma
(metabolism)
- Cytochrome P-450 CYP1A2
(genetics)
- Cytochrome P-450 CYP2E1
(genetics)
- Genotype
- Humans
- Pharmacogenetics
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Polymorphism, Restriction Fragment Length
- Theophylline
(blood, metabolism)
- Uric Acid
(analogs & derivatives, blood)
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