Pharmacogenetic Landscape of DPYD Variants in South Asian Populations by Integration of Genome-Scale Data

Abstract

Aim: Adverse drug reactions to 5-Fluorouracil(5-FU) is frequent and largely attributable to genetic variations in the DPYD gene, a rate limiting enzyme that clears 5-FU. The study aims at understanding the pharmacogenetic landscape of DPYD variants in south Asian populations. Materials & methods: Systematic analysis of population scale genome wide datasets of over 3000 south Asians was performed. Independent evaluation was performed in a small cohort of patients. Results: Our analysis revealed significant differences in the the allelic distribution of variants in different ethnicities. Conclusions: This is the first and largest genetic map the DPYD variants associated with adverse drug reaction to 5-FU in south Asian population. Our study highlights ethnic differences in allelic frequencies.

Keywords::

• 5-FU toxicity
• allele frequency
• DPYD
• drug-related side effects and adverse reactions
• pharmacogenomics
• south Asia

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/pgs-2017-0101

Acknowledgements

The authors are thankful to all the participating subjects for their support and cooperation in carrying out the study. The authors acknowledge constructive criticism and suggestions from A Sivadas and R Koshy.

Financial & competing interests disclosure

This study was supported and funded by the Council of Scientific and Industrial Research (CSIR), through Wellness Genomics Project (BSC0212). Data for the INDICO cohort was generated with support by grant CARDIOMED (BSC0122). The data for pharmacogenetic variants were funded through grant GOMED (MLP1601). The granting agencies had no role in the preparation of the manuscript or decision to publish. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported and funded by the Council of Scientific and Industrial Research (CSIR), through Wellness Genomics Project (BSC0212). Data for the INDICO cohort was generated with support by grant CARDIOMED (BSC0122). The data for pharmacogenetic variants were funded through grant GOMED (MLP1601). The granting agencies had no role in the preparation of the manuscript or decision to publish. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript