Relationship Between CYP1A2 Polymorphism And The Theophylline Metabolism In COPD Patients Of Uygur Nationality

Objective: To investigate whether CYP1A2 gene polymorphism and COPDUygur theophylline adverse reactions whether or not.Methods:(1)Patients who meet the selected criteria are screened for a 1-week trial flow.Patient first visit signed informed consent,fill out the case report form(CRF).(2)Pharmacists for each patient were selected for detailed medication explanation,fill in the case report form,record the patient during the test medication.Patients were prohibited from taking alcohol,tea,coffee and caffeinated beverages throughout the trial.Other medications were treated as usual.However,if the condition requires the use of drugs that may affect the metabolism of theophylline,then the data for that case should be discarded.(3)Fasting blank blood samples collected in the EDTA anticoagulant tubes,while blood tests,liver and kidney function and lung function tests.Screening patients with doxofylline 0.3g qd intravenous infusion,continuous use for 1 week.1 week after taking the drug in the morning fasting elbow venous blood 2mL in EDTA anticoagulant tube.Blood samples were centrifuged at 3000 rpm for 10 min,blood cells and plasma were separated,and stored at-80 ℃ for storage.(4)Blood cells were used for gene sequencing,and plasma was used for theophylline and metabolite concentrations.Result:(1)Fifty elderly Uygur COPD patients taking theophylline sustained-release capsules 100mg/time,the concentration of theophylline in serum was determined to be 3.45±2.0μg/ml after 2/day plasma concentration was stable.Gender had no effect on the plasma concentration of theophylline(P>0.05).the results of blood drug concentration in patients older than 70 years and those aged less than 70 years were statistically different(P < 0.05).According to the nature of work groups,divided into two group,party,government organs staff,farmers and workers,the theophylline blood concentrations were 2.629 ± 1.171 ug/ml and 3.409 ± 1.563 ug/ml,and between the two groups were statistically analyzed,which indicates that has a significant difference between the two groups(P < 0.05).(2)The mutation rate of2467delT(CYP1A2*1D),-163C>A(CYP1A2*1F)in 158 patients with COPD was21.84% and 70.25%,respectively.A comparison of Asians and Caucasians,respectively,found that the frequency of-2467delT(CYP1A2*1D)mutation was significantly higher in Uygur patients than in Caucasians and Asians(P < 0.05).the mutation frequency of CYP1A2-163C>A is relatively high in all ethnic groups in the world.however,the mutation rate of Uygur gene was significantly higher than that of Caucasian(P < 0.05).(3)The study found that the-2467 del T(CYP1A2*1D)siteand-163C>A(CYP1A2*1F)site of the CYP1A2 gene had no effect on the difference in serum theophylline concentration.Conclusion:(1)According to the patient’s theophylline plasma concentration and condition,providing individualized dosing regimen can effectively reduce the toxic side effects of theophylline.(2)It is inferred that age profession and occupation may be factors that affect plasma theophylline concentration in patients and gender,weight,and BMI may not be.(3)The-2467delT(CYP1A2*1D)and-163C>A(CYP1A2*1F)locus may not be factors that influence the metabolism of theophylline.