Variation in 100 relevant pharmacogenes among emiratis with insights from understudied populations

Abstract

Genetic variations have an established impact on the pharmacological response. Investigating this variation resulted in a compilation of variants in “pharmacogenes”. The emergence of next-generation sequencing facilitated large-scale pharmacogenomic studies and exhibited the extensive variability of pharmacogenes. Some rare and population-specific variants proved to be actionable, suggesting the significance of population pharmacogenomic research. A profound gap exists in the knowledge of pharmacogenomic variants enriched in some populations, including the United Arab Emirates (UAE). The current study aims to explore the landscape of variations in relevant pharmacogenes among healthy Emiratis. Through the resequencing of 100 pharmacogenes for 100 healthy Emiratis, we identified 1243 variants, of which 63% are rare (minor allele frequency ≤ 0.01), and 30% were unique. Filtering the variants according to Pharmacogenomics Knowledge Base (PharmGKB) annotations identified 27 diplotypes and 26 variants with an evident clinical relevance. Comparison with global data illustrated a significant deviation of allele frequencies in the UAE population. Understudied populations display a distinct allelic architecture and various rare and unique variants. We underscored pharmacogenes with the highest variation frequencies and provided investigators with a list of candidate genes for future studies. Population pharmacogenomic studies are imperative during the pursuit of global pharmacogenomics implementation.

Pharmacogenomics implementation in cardiovascular disease in a highly diverse population: initial findings and lessons learned from a pilot study in United Arab Emirates

“…This observation is aligned with the situation of genomic research in general [12]. Few efforts have been carried out to bridge this gap in the field of PGx [13,14]. In comparison, scarce, if any, PGx-clinical implementation research has been carried out in populations other than those of Caucasian descent and, to a much lesser extent, people from East Asia [15].…”

Pharmacogenomics in Psychiatry Practice: The Value and the Challenges

“…The highest detected diplotype was the CYP4F2*1/*3 (54%), while CYP2B6*1/*18, CYP2C9*2/*3 (1%) were the lowest among the CYP family. Moreover, although the detected SNP for ABCC4 had the highest allele frequency (rs1751034, 82.6%), among the CYP family identified in the current group, in a descending order of allele frequency, CYP4F2 had the highest allele frequency (rs2108622, 45.92%), followed by CYP2B6 (rs3745274, 31%), CYP2C19 (rs4244285, 15.1%), CYP2C8 (rs10509681, 13.64%), CYP2C9 (rs1057910, 7.07%), CYP2C8 (rs7900194, 2%), and CYP2B6 (rs28399499, 1.01%) [ 147 ].…”

“…In another study conducted in association with the SEAPharm consortium project [ 146 ], Al-Mahayri et al [ 147 ] analyzed the landscape of variation among the indigenous citizens of the United Arab Emirates through targeted resequencing. The DNA from 100 self-identified Emirati participants was extracted from whole blood samples and was resequenced by utilizing the targeted sequencing panel (PKSeq).…”

Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk

“…Literature evidence shows that the G to A change leads to an Arg213His replacement in the sulfotransferase gene, which reduces 85% enzyme activity [ 29 ]. Since this gene is involved in the transformation of procarcinogens, the presence of SNPs may lead to aberrant activity and carcinogenic developments [ 30 ].…”