A population study of clinically actionable genetic variation affecting drug response from the Middle East
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عرض / فتح
التاريخ
2022المؤلف
Jithesh, Puthen VeettilAbuhaliqa, Mohammed
Syed, Najeeb
Ahmed, Ikhlak
El Anbari, Mohammed
Bastaki, Kholoud
Sherif, Shimaa
Umlai, Umm-Kulthum
Jan, Zainab
Gandhi, Geethanjali
Manickam, Chidambaram
Selvaraj, Senthil
George, Chinnu
Bangarusamy, Dhinoth
Abdel-latif, Rania
Al-Shafai, Mashael
Tatari-Calderone, Zohreh
Estivill, Xavier
Pirmohamed, Munir
Abdel-latif, Rania
Saqri, Tariq Abu
Zaid, Tariq Abu
Afifi, Nahla
Al-Ali, Rashid
Al-Khodor, Souhaila
Al-Muftah, Wadha
Al-Sarraj, Yasser
Albagha, Omar
Alkhayat, Eiman
Alkuwari, Fatima
Almabrazi, Hakeem
Alshafai, Mashael
Althani, Asmaa
Alvi, Muhammad
Badii, Ramin
Badji, Radja
Chouchane, Lotfi
Darwish, Dima
El Khouly, Ahmed
Ennaifar, Maryem
Estivill, Xavier
Fadl, Tasnim
Fakhro, Khalid
Fethnou, Eleni
Hamza, Mehshad
Ismail, Said I.
Jithesh, Puthen V.
Khatib, Mohammedhusen
Liu, Wei
Lorenz, Stephan
Mbarek, Hamdi
Mokrab, Younes
Pathare, Tushar
Poolat, Shafeeq
Qafoud, Fatima
Vempalli, Fazulur Rehaman
Saad, Chadi
Suhre, Karsten
Syed, Najeeb
Tatari, Zohreh
Temanni, Ramzi
Tomei, Sara
Yasin, Heba
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البيانات الوصفية
عرض كامل للتسجيلةالملخص
Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs. We also performed a focused analysis of genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predicted their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or class of drugs were significantly different between the Qatari population and other world populations. On average, Qataris carry 3.6 actionable genotypes/diplotypes, affecting 13 drugs with guidelines for clinical implementation, and 99.5% of the individuals had at least one clinically actionable genotype/diplotype. Increased risk of simvastatin-induced myopathy could be predicted in ~32% of Qataris from the diplotypes of SLCO1B1, which is higher compared to many other populations, while fewer Qataris may need tacrolimus dosage adjustments for achieving immunosuppression based on the CYP3A5 diplotypes compared to other world populations. Distinct distribution of actionable pharmacogenomic variation was also observed among the Qatari subpopulations. Our comprehensive study of the distribution of actionable genetic variation affecting drugs in a Middle Eastern population has potential implications for preemptive pharmacogenomic implementation in the region and beyond. 2022, The Author(s).
المجموعات
- العلوم الحيوية الطبية [692 items ]