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

Abstract

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]

Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

“… found CYP1A2*1C polymorphism was associated with reduced theophylline clearance in Japanese asthma patients (non‐smokers), and Uslu et al . reported that CYP1A2*1D and CYP1A2*1F were significantly associated with altered theophylline concentration in Turkish patients. Because both frequency spectrums of SNPs and haplotype structures at CYP1A2 are different between different ethnics, these results were not contradictory to ours.…”

“…Uslu A et al . reported that CYP1A2*1D was significantly associated with theophylline metabolism in Turkish patients . However, another study in Japanese patients reported that there was no influence of CYP1A2*1C and CYP1A2*1F on the theophylline metabolic ratio .…”

Pilot Study on Genetic Polymorphisms CYP1A2*1F on Asthma Patients and Nonasthma in Indonesia

“…14,15 Oleh karena itu, diperlukan penelitian yang lebih lanjut mengenai farmakogenomik untuk mengetahui efek obat yang dipengaruhi oleh genetik karena respons obat dapat ditentukan oleh hubungan antara genotipe. [16][17][18][19] Beberapa studi terdahulu terhadap ras yang berbeda telah menunjukkan bahwa efek polimorfisme gen CYP1A2 memengaruhi metabolisme teofilin pada pasien asma yang menggunakan teofilin atau aminofilin sebelumnya sehingga akan memengaruhi kadar teofilin dalam darah. 17,18 Hal ini dapat memengaruhi keamanan obat tersebut dan risiko terhadap terjadinya ADR.…”

“…[16][17][18][19] Beberapa studi terdahulu terhadap ras yang berbeda telah menunjukkan bahwa efek polimorfisme gen CYP1A2 memengaruhi metabolisme teofilin pada pasien asma yang menggunakan teofilin atau aminofilin sebelumnya sehingga akan memengaruhi kadar teofilin dalam darah. 17,18 Hal ini dapat memengaruhi keamanan obat tersebut dan risiko terhadap terjadinya ADR. Identifikasi dan karakterisasi sejumlah besar polimorfisme genetik (biomarker) dalam enzim metabolisme obat dan transporter obat dalam etnis berbagai kelompok individu dapat memberikan pengetahuan substansial tentang mekanisme antarindividu dalam menanggapi obat.…”

Genetic predictors of theophylline efficacy and safety in children with bronchial asthma

“…Показано, что клиренс теофиллина достоверно меньше у носителей аллельного варианта G2964A CYP1A2, с генотипами GA или АА, ассоциированными с медленной скоростью метаболизма лекарственных средств-субстратов [6,10]. Доказано влияние полиморфизма гена CYP1A2 на метаболизм теофиллина и формирование хронической обструктивной болезни лёгких [13,14] При изучении равновесного распределения частот изучаемых генотипов по полиморфному маркёру было установлено, что группа исследования (n=250) соответствует равновесию Харди-Вайнберга (p >0,05). Это позволяет сделать вывод о репрезентативности выборки и достоверности полученных результатов.…”