Document Details

Document Type : Thesis 
Document Title :
POLYMOORPHISM OF GENES INVOLVED IN BISOPROLOL RESPONSE IN PATIENTS WITH CARDIAC DISEASE ATTENDING KING ABDULAZIZ UNIVERSITY HOSPITAL.
تعدد اشكال الجينات المسؤولة عن استجابة عقار البسوبرولول في المصابين بأمراض القلب في مستشفى جامعة الملك عبد العزيز
 
Subject : Faculty of Medicine 
Document Language : Arabic 
Abstract : Bisoprolol is a selective β1-blocker, a class of drugs used primarily in cardiovascular diseases. β – Blockers are one of most important medications, and among the most widely prescribed of all drug classes. They are recommended as first line to treat patients with numerous diseases such as hypertension, angina, and heart failure. Bisoprolol is 50% metabolized in the liver and 50 % is excreted unchanged via the kidney. Previous studies showed that the response to bisoprolol often produces variable response among patients. This phenomenon may be due to genetic variation. Therefore, the present study is conducted to investigate the possible gene polymorphisms in cytochrome P450 (CYP) 2D6 responsible for bisoprolol pharmacokinetics and correlate this defect with the drug response or adverse effects in patients taking this drug attending King Abdulaziz University Hospital. Patients and methods: A total of 107 patients were enrolled in the study. Five ml of venous blood was collected from each patient and genotyping for CYP2D6*2A (rs1080985) and CYP 2D6*10 (rs1065852) using Custom Taqman® was done. Response to bisoprolol was evaluated through assessment of diastolic and systolic blood pressure and by measuring bisoprolol plasma level using triple quad mass spectrometer (TQ-MS). Results: All patients were found to carry homozygous CYP 2D6*10 (GG) and none were carrying heterozygous (GA) or homozygous (AA) genotype. CYP 2D6*2A genotyping detected homozygote GG in 70 (65.4%) out of 107 patients, the heterozygote GC in 19 (17.7%) patients, and the homozygote CC in 18 (16.8%) patients with minor allele frequency (MAF) of 0.257. The mean plasma concentration of bisoprolol in CYP 2D6*2A allele CC carriers was (11.9 ±4.4 ng/ml) and increased by 19.3% when compared to GG carriers (14.2 ±5.6 ng/ml). This resulted in a decrease in both systolic and diastolic blood pressure by 7% and 8% respectively. Similarly the mean plasma concentration of bisoprolol in CYP2D6*2A heterozygous GC carriers was 21.5 ±8.1 ng/ml, an increase by 81% compared to homozygous CC carriers. This resulted in a decrease in both systolic and diastolic blood pressure by 16% and 9% respectively. Analysis of CYP2D6*2A genotype in patients suffered from bisoprolol side effects revealed that they were either homozygous GG carriers or heterozygous GC carriers. None of the patients who suffered from side effects were homozygous CC carriers. Conclusion: The result of the present study shows a possible association between CYP2D6*2A genotype and bisoprolol response. It is concluded that patients who are homozygous GG carriers and heterozygous GC carriers might have a better response to bisoprolol in systolic and diastolic blood pressure than homozygous CC carriers. However, patients who are homozygous CC carriers have less chance to be affected by bisoprolol side effects. The study opens a new window for studying more single nucleotide polymorphisms (SNPs) for CYP2D6 and to define the role of various SNPs in inter-individual variability in bisoprolol response. 
Supervisor : Prof. Zoheir Abdullah Damanhouri 
Thesis Type : Master Thesis 
Publishing Year : 1440 AH
2019 AD 
Co-Supervisor : Dr. Huda Mohammed Alkreathy 
Added Date : Tuesday, August 27, 2019 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
خلود محمد السيدAlsayyid, Khlood MohammedResearcherMaster 

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