CHARACTERIZATION OF SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH RESPONSE TO ANTIDEPRESSANT DRUGS IN SUDANESE POPULATION
Authors name: Suaad Balla khalaf alla , Mohamed O Elsiddeig, Muntaser Eltyeb Ibrahim
Affiliation: Institute of Endemic Disease – University of Khartoum.
Background: Antidepressant drugs [AD] prescribed for major depressive disorders are associated with therapeutic failures in approximately 40% of patients after initial dosing. Pharmacogenetic (PGx) variances play a significant role in these failures and therefore, using genetic data in decision-making for population-based dosing may both enhance efficacy and reduce adverse effects. Prior knowledge of allele distributions of the (PGx) biomarkers in different countries can help towards patient stratification for most populations during the drug prescribing process. However, Allele frequency distributions for gene polymorphisms associated with [AD] response in the Sudanese population and Africa in general remains largely not characterized.
Objective: To investigate single nucleotide Polymorphisms [SNPs] affecting several pharmacodynamic and pharmacokinetic variables associated with response to [AD] in Sudanese and to compare the data with the global geographical data reported in gnomAD genome database from different ethnic populations.
Design: Out of 764 SNPs in 7 candidate genes affecting response to [AD] in 242 healthy Sudanese individuals genotype data, a total of 46 SNPs chosen according to deleteriousness and clinical annotation reported in PharmGKB database. Minor allele frequency (MAF) of clinically actionable SNPs compared with gnomaAD genome population frequencies using Chi-square test.
Result: Among deleterious SNPs, nine are unreported in gnomad genome database, two SNPs were common, MAF>5%, SLC6A4 rs138004662 (8%) and ABCB1 rs2032582 (15%). Of the clinically actionable variants, 3 SNPs (ABCB1 rs1045642, rs2032582, and BDNF rs7103411) show significant differences (p-value <0.05) between Sudanese and all other populations with the lowest frequency in Sudanese. ABCB1 rs1272006 was monomorphic (that is, no variation) across all population tested. 2 SNPs (rs7103411 and rs7124442) associated with better response to citalopram is less common in Sudanese compared with other populations.
Conclusion: Since therapeutic decision relies mainly on the US FDA or European Medical Agency guidelines for dosing instructions, understanding of the inter-ethnic differences in the pharmacogenetic is critical to guide more effective global drug prescriptions, Such data will be useful for future clinical and for drug dosage recommendations in the Sudanese population.
Keywords: Antidepressant, SNP, Pharmacogenetics.
Presenter name: Suaad Balla Khalafalla Abdalla
Affiliations: Institute of Endemic Diseases- University of Khartoum.