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Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma
Author(s) -
Obase Yasushi,
Shimoda Terufumi,
Kawano Tetsuya,
Saeki Sachiko,
Tomari Shinya,
MitsutaIzaki Kazuko,
Matsuse Hiroto,
Kinoshita Moritoshi,
Kohno Shigeru
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00013-4
Subject(s) - cyp1a2 , theophylline , genotype , allele , polymorphism (computer science) , asthma , intron , gene , endocrinology , medicine , chemistry , pharmacology , cytochrome p450 , metabolism , biology , genetics
Background Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in theophylline metabolism. Objective We analyzed the effect of genetic polymorphisms in the 5′‐flanking region to the first intron of the CYP1A2 gene on theophylline metabolism in 75 Japanese patients with asthma and 159 healthy Japanese volunteers. Methods Genetic polymorphisms were detected at 4 sites of the CYP1A2 gene, −2964(G/A) and −1569(T/del) in the 5′‐flanking region and 155(T/G) and 731(A/C) in the first intron. Results There were no significant differences in the distribution of gene polymorphisms between the asthmatic and control groups. Among asthmatic patients, theophylline clearance was significantly lower in patients with the polymorphism at site −2964(G/A) whose genotype was G/A (0.029 ± 0.001 L · h −1 · kg −1 ) or A/A (0.029 ± 0.002 L · h −1 · kg −1 ) than in those whose genotype was G/G (0.034 ± 0.001 L · h −1 · kg −1 ) ( P < .01 and P < .05, respectively). High theophylline clearance levels significantly correlated with age in the G/G subgroup of site −2964(G/A) ( P < .05, r = −0.35) but not in the G/A or A/A subgroup. Conclusion Given its potential side effects, theophylline may need to be used with care in patients with the A allele at site −2964(G/A) in the CYP1A2 gene, because theophylline metabolism levels are lower in such patients, particularly in young asthmatic individuals. Clinical Pharmacology & Therapeutics (2003) 73 , 468–474; doi: 10.1016/S0009‐9236(03)00013‐4