Authors: Yeomin Yoon HyungDoo Park Kyoung Un Park Jin Q Kim YoonSeok Chang Junghan Song
Publish Date: 2006/07/14
Volume: 62, Issue: 8, Pages: 627-631
Abstract
Theophylline is metabolized to 13dimethyluric acid 13DMU 3methylxanthine and 1methylxanthine by CYP1A2 and partly by CYP2E1 Because 13DMU is the major metabolite of theophylline the 13DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance Here we investigated the associations between 13DMU/theophylline ratios and genetic polymorphisms of CYP2E1 and CYP1A2Polymerase chain reaction PCR and direct sequencing or PCRrestriction fragment length polymorphism RFLP were performed to analyze CYP2E1 and CYP1A2 promoter polymorphisms in 62 Korean asthma patients Plasma theophylline and 13DMU levels were measured by liquid chromatographytandem mass spectrometryEleven polymorphisms including Ins96 −1566 TA −1515 TG −1414 CT −1295 GC −1055 CT −1027 TC −930 AG −807 TC −352 AG and −333 TA 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 TA −1295 GC −1055 CT −1027 TC and −807 TC were closely linked Another three polymorphisms Ins96 −930 AG and −352 AG and two polymorphisms −1515 TG and −333 TA were also closely linked The five closely linked polymorphisms were associated with significantly different 13DMU/theophylline ratios between heterozygotes plus homozygotes of a rare allele n=23 00368±00171 and common allelic homozygotes n=39 00533±00343 p=0024 by MannWhitney U test In the CYP1A2 gene the −2964GA polymorphisms exhibited a significant difference in 13DMU/theophylline levels between heterozygotes plus homozygotes of a rare allele n=30 00406±00272 and homozygotes of a common allele n=32 00534±00316 p=0032
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