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; DPYD; allele frequency; drug-related side effects and adverse reactions; pharmacogenomics; south Asia.