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

Obase, Yasushi; Shimoda, Terufumi; Kawano, Tetsuya; Saeki, Sachiko; Tomari, Shinya; Mitsuta-Izaki, Kazuko; Matsuse, Hiroto; Kinoshita, Moritoshi; Kohno, Shigeru

doi:10.1016/s0009-9236(03)00013-4

Cited by 71 publications

(48 citation statements)

References 14 publications

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“…No significant association has been found between CYP1A2 enzymatic activity and CYP1A2 variants (CYP1A2*1C and CYP1A2*1F) in the mentioned study (17). Contrarily, CYP1A2*1C has been associated with altered TP metabolism in asthmatic Japanese patients in another study (18). In our study, the COPD patients had a higher prevalence of the CYP1A2*1D "T" allele and the CYP1A2*1F "C" allele compared to the control group.…”

Section: Resultscontrasting

confidence: 67%

The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

Uslu

Öğüş

Özdemir³

et al. 2010

BMB Reports

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Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in the metabolism of theophylline (TP). We aimed to investigate the effect of CYP1A2*1C, CYP1A2*1D, CYP1A2*1E, and CYP1A2*1F polymorphisms of the CYP1A2 on TP metabolism by PCR-RFLP in 100 Turkish patients with chronic obstructive pulmonary disease (COPD) receiving TP. One hundred and one healthy volunteers were included as control group. The genotype frequencies of the CYP1A2*1D and CYP1A2*1F were found to be significantly different in the patients compared to the controls. The "T" allele at -2467 delT and the "C" allele at -163 C ＞ A in the CYP1A2 displayed association with a significantly increased risk for COPD. "T" allele at -2467 delT was also associated with a high risk of disease severity in COPD. In conclusion, our data suggest that genetic alterations in CYP1A2 may play a role both in the pharmacogenetics of TP and in the development of COPD.[BMB reports 2010; 43(8): 530-534]

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Section: Resultscontrasting

confidence: 67%

The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

Uslu

Öğüş

Özdemir³

et al. 2010

BMB Reports

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“…29 Dose-related toxicities, such as tachycardia, headache, nausea, and 55 Obase et al 56 have recently described a common promoter polymorphism in the CYP1A2 gene that is associated with altered clearance of theophylline. Specifically, the A allele of a G/A SNP at position À2964 was associated with decreased clearance (increased serum levels) in a group of 75 Japanese asthmatics.…”

Section: Cyp1a2 Polymorphisms and Theophylline Metabolismmentioning

confidence: 99%

“…Serum levels must be monitored closely because of a narrow therapeutic window and a plethora of drug interactions 29 may have anti-inflammatory effects, however, that may not necessitate monitoring. 55 Obase et al 56 have recently described a common promoter polymorphism in the CYP1A2 gene that is associated with altered clearance of theophylline. Specifically, the A allele of a G/A SNP at position À2964 was associated with decreased clearance (increased serum levels) in a group of 75 Japanese asthmatics.…”

Section: Cyp1a2 Polymorphisms and Theophylline Metabolismmentioning

confidence: 99%

Overview of the pharmacogenetics of asthma treatment

et al. 2006

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Asthma affects approximately 300 million individuals worldwide. Medications comprise a substantial portion of asthma expenditures. Despite the availability of three primary therapeutic classes of medications, there are a significant number of nonresponders to therapy. Available data, as well as previous pharmacogenetic studies, suggest that genetics may contribute as much as 60-80% to the interindividual variability in treatment response. In this methodologic review, after providing a broad overview of the asthma pharmacogenetics literature to date, we describe the application of a novel family-based screening algorithm to the analysis of pharmacogenetic data and highlight our approach to identifying and verifying loci influencing asthma treatment response. This approach seeks to address issues related to multiple comparisons, statistical power, population stratification, and failure to replicate from which previous population-based or case-control pharmacogenetic association studies may suffer. Identification of such replicable loci is the next step towards the goal of 'individualized therapy' for asthma. The Pharmacogenomics Journal (2006) 6, 311-326. doi:10.1038/sj.tpj.6500387; published online 25 April 2006Keywords: beta-agonist; leukotriene; corticosteroid; FEV 1 ; genetics IntroductionThe goal of this review is to give a comprehensive assessment of asthma pharmacogenetics and highlight the scientific approach being taken by the pharmacogenetics of asthma treatment (PHAT) research group (http:// www.pharmgat.org/) to this research area. Our approach strives to address many of the potential problems inherent in genetic association studies, including those related to multiple comparisons, lack of statistical power, population stratification, and failure to replicate. Moreover, our group of collaborative investigators is well positioned to investigate the molecular biology and functional genomics of identified candidate gene associations. In this review, we will cover some aspects of asthma health care, pathobiology, and review the available pharmacogenetics literature on the important types and pathways of asthma medications: b-agonists, leukotriene (LT) antagonists, methylxanthines, and corticosteroids. We will then present details of our research approach to finding replicated pharmacogenetic associations and suggest what the future may hold for this research area. Pharmacogenetics -definition and rationalePharmacogenetics is the study of the role of genetic determinants in the variable, interindividual response to medications. Numerous examples of heritable differences in pharmacokinetics (drug distribution and metabolism) in The Pharmacogenomics Journal (2006) 6, 311-326 & 2006 Nature Publishing Group All rights reserved 1470-269X/06 $30.00 www.nature.com/tpj individuals resulting in varied clinical response to medications have been described. 1 Other mechanisms underlying the genetic response to drugs includes alterations in pharmacodynamics (changes in the drug target), idiosyncratic associations (unin...

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“…1 Teofilin diekskresi ke dalam ASI, dan diperkirakan <1% dari dosis yang dikonsumsi oleh seorang wanita hamil akan diekskresikan ke dalam ASI sehingga memengaruhi infant di dalam kandungan; 35 (c) Gangguan pada fungsi hati. Pasien dengan kongesti hati atau gagal hati menunjukkan penurunan klirens teofilin yang signifikan dan t1/2 yang lebih panjang; 30 (d) Merokok atau berhenti merokok <2 tahun, karena merokok memengaruhi kadar teofilin dalam darah, 36 yang memiliki pengaruh kuat terhadap aktivitas CYP1A2; 37 (e) Konsumsi kopi atau kafein. Kafein merupakan salah satu golongan metilsantin (selain teofilin dan aminofilin yang dapat bersumber dari teh, kopi, dan cokelat), yang dapat memengaruhi sistem saraf pusat, ginjal, otot jantung dan rangka.…”

Section: Pembahasanunclassified

Effectiveness and Toxicity Risk of Intravenous Aminophylline in Exacerbation Asthma Treatment

Lorensia

Ikawati

Andayani

et al. 2018

Indones J Clin Pharm

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4Program Studi Apoteker, Fakultas Farmasi Universitas Surabaya, Surabaya AbstrakAsma merupakan penyakit inflamasi kronis pada saluran pernafasan yang mempunyai prevalensi global yang cukup besar. Perburukan penyakit asma berupa serangan asma yang menyebabkan peningkatan gejala asma dan penurunan fungsi paru secara progresif. Salah satu obat asma yang masih sering digunakan di Indonesia adalah aminofilin intravena. Aminofilin merupakan obat dengan rentang terapi sempit yang berisiko menyebabkan toksisitas obat, namun data perbandingan keuntungan efektivitas dan keamanan obat tersebut belum memadai. Penelitian ini bertujuan untuk mengetahui efektivitas aminofilin intravena pada pengobatan awal serangan asma berupa perbaikan gejala asma dan kejadian toksisitas terkait gejala yang muncul dan kadar teofilin dalam darah di suatu rumah sakit di Surabaya, Indonesia. Penelitian ini menggunakan metode pra-eksperimental yang dilaksanakan sejak 2014 hingga 2016. Sebanyak 27 pasien terlibat dalam penelitian ini. Terapi yang diberikan adalah aminofilin intravena selama satu jam. Metode sampling yang digunakan adalah consecutive sampling dengan teknik analisis deskriptif dan jum. Semua subjek penelitian menunjukkan perbaikan gejala serangan asma dengan terapi aminofilin intravena selama satu jam, dan tidak ada yang mengalami toksisitas karena kadar teofilin dalam darah di bawah rentang terapi. Aminofilin masih efektif dalam mengurangi gejala pada serangan asma dan tidak menunjukkan risiko toksisitas.Kata kunci: Aminofilin, efektivitas, serangan asma, toksisitas Effectiveness and Toxicity Risk of Intravenous Aminophylline in Exacerbation Asthma Treatment AbstractAsthma is a chronic inflammatory disease in the respiratory tract that has a considerable global prevalence. The worsening of asthma is an asthma attack that causes asthma symptoms to increase and decreased lung function progressively. One of the most commonly used asthma medications in Indonesia is intravenous aminophylline. Aminophylline is a drug with a narrow range of therapies that is at risk of causing drug toxicity, but the comparative data on the efficacy and safety benefits of the drug are inadequate. This study aimed to determine the effectiveness of aminophylline intravenously in the early treatment of asthma attacks in the form of improvements in asthma symptoms and toxicity events related to the symptoms that appear and blood theophylline levels in a hospital in Surabaya, Indonesia. This study used a pre-experimental method which was carried out from 2014 to 2016. A total of twenty seven patients were involved in the study. The therapy given was aminophylline intravenously for one hour. The sampling method used was consecutive sampling with descriptive analysis technique. All subjects showed improved symptoms of asthma attacks with intravenous aminophylline therapy for one hour, and none had toxicity due to theophylline levels in the blood below the therapeutic range. Aminophylline is still effective in reducing symptoms in asthma attacks and does not indic...

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Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma

Abstract: 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.

Cited by 71 publications

References 14 publications

The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

Overview of the pharmacogenetics of asthma treatment

Effectiveness and Toxicity Risk of Intravenous Aminophylline in Exacerbation Asthma Treatment

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