Polymorphisms in the <i>CYP1A2</i> gene and theophylline metabolism in patients with asthma

• Yasushi Obase

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Terufumi Shimoda

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Tetsuya Kawano

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Sachiko Saeki

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Shin‐ya Tomari

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Kazuko Mitsuta‐Izaki

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Hiroto Matsuse

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Moritoshi Kinoshita

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

• Shigeru Kohno

  Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and Otsuka Assay Laboratories, Otsuka Pharmaceutical Co Tokushima Japan

抄録

Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in theophylline metabolism. 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. 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. 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. 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: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1016/S0009-9236(03)00013-4">10.1016/S0009‐9236(03)00013‐4

収録刊行物

• Clinical Pharmacology & Therapeutics

  Clinical Pharmacology & Therapeutics 73 (5), 468-474, 2003-05

  Wiley

キーワード

• Pharmacology (medical)
• Pharmacology

詳細情報

• CRID: 1360292618727378688
• NII論文ID: 30016991330
• DOI: 10.1016/s0009-9236(03)00013-4
• ISSN: 15326535
• ISSN: 00099236
• Web Site: https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1016/S0009-9236%2803%2900013-4
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