Pharmacogenetic landscape of DPYD variants in south Asian populations by integration of genome-scale data. (February 2018)

• Record Type: Journal Article
• Authors: Hariprakash, Judith M; Vellarikkal, Shamsudheen K; Keechilat, Pavithran; Verma, Ankit; Jayarajan, Rijith; Dixit, Vishal; Ravi, Rowmika; Senthivel, Vigneshwar; Kumar, Anoop; Sehgal, Paras; , Aradhana; Sonakar, Akhilesh K; Ambawat, Sakshi; Giri, Anil K; Philip, Arun; Sivadas, Akhila; Faruq, Mohammed; Bharadwaj, Dwaipayan; Sivasubbu, Sridhar; Scaria, Vinod
• Is Part Of: Pharmacogenomics. Volume 19:Number 3(2018)
• Page Start: 227
• Page End: 241
• Publication Date: 2018-02
• Subjects: 5-FU toxicity -- allele frequency -- DPYD -- drug-related side effects and adverse reactions -- pharmacogenomics -- south Asia; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2017-0101
• Languages: English
• ISSNs: 1462-2416

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.