PHARMACOGENETICS OF FLUOROPYRAMIDINES

PHARMACOGENETICS OF FLUOROPYRAMIDINES

PHARMACOGENETICS OF FLUOROPYRAMIDINES: ANALYSIS OF DPYD SNPS IN THE SUDANESE POPULATION

Sabah Alrasheed Abdalaziz Alhaj1, Mohammed Omar Elsiddieg Abdallah2, Muntaser Ibrahim3   

  1. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, P. O. Box 102, ArmyRoad, 11111 Khartoum, Sudan, Sabahalhaj1991@gmail.com
  2. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, P. O. Box 102, Army Road, 11111 Khartoum, Sudan, melsiddieg@gmail.com
  3. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, P. O. Box 102, Army Road, 11111 Khartoum, Sudan, mibrahim@iend.org

 

Aim: To contribute towards the DPYD gene database and the Pharmacogenetics Sudanese database reporting for the first time, the frequency and type of sequence variations in the DPYD gene among the Sudanese population.  Furthermore, we aim to analyze the variation spectrum in the DPYD gene by comparing the reported Sudanese frequencies with the global population’s frequencies.

Background: Pharmacogenetics and pharmacogenomics (PGx) researches aim to elucidate the genetic basis for the inter-individual differences in drug response. fluoropyrimidines are among the most frequently prescribed anticancer drugs. Variant analysis of DPYD gene that codes for their key catabolism enzyme may help to predict fluoropyrimidine-related severe toxicity.

Methods: Publicly available genotype array data were analyzed for 242 Sudanese individuals encompassing 18 sub-populations. We reported the frequencies of DPYD variants that had >20 CADD score for further functional analysis. In addition, a total of 38 clinically relevant variants from the DPYD PharmGKB database were extracted and looked for in our data to report their frequencies and compare them with global populations from the gnomAD database.

Results: Of the 1219 variants analyzed, 11 have CADD score > 20. Of the 38 variants, 6 were found in our study population and significant statistical differences were found in the distribution of most of these variants when compared to the global population’s frequencies.

Conclusions: Different variation spectrum is found in the DPYD variants among Sudanese compared with other global populations. Further pharmacogenetic studies are required to investigate and document pharmacogenetic variants in DPYD and other metabolizing enzymes genes to help impact clinical practice.

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