Pharmacogenetic landscape of DPYD variants in south Asian populations by integration of genome-scale data

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. Systematic analysis of popul...

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Bibliographic Details
Published in:Pharmacogenomics 2018-02, Vol.19 (3), p.227-241
Main Authors: Hariprakash, Judith M, Vellarikkal, Shamsudheen K, Keechilat, Pavithran, Verma, Ankit, Jayarajan, Rijith, Dixit, Vishal, Ravi, Rowmika, Senthivel, Vigneshwar, Kumar, Anoop, Sehgal, Paras, Sonakar, Akhilesh K, Ambawat, Sakshi, Giri, Anil K, Philip, Arun, Sivadas, Akhila, Faruq, Mohammed, Bharadwaj, Dwaipayan, Sivasubbu, Sridhar, Scaria, Vinod
Format: Article
Language:English
Subjects:
5-Fluorouracil
Adolescent
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic - toxicity
Apoptosis
Asian Continental Ancestry Group - genetics
Asian people
Cancer therapies
Chemotherapy
Cohort Studies
Consortia
Datasets
Dehydrogenases
Diabetes
Dihydrouracil Dehydrogenase (NADP) - genetics
Drug-Related Side Effects and Adverse Reactions - enzymology
Drug-Related Side Effects and Adverse Reactions - etiology
Drug-Related Side Effects and Adverse Reactions - genetics
Enzymes
European Continental Ancestry Group - genetics
Female
Fluorouracil - toxicity
Gene Frequency
Genetic diversity
Genomes
Genotype & phenotype
Humans
Male
Middle Aged
Pharmacogenetics
Polymorphism, Single Nucleotide
Population genetics
Population studies
Studies
Young Adult
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Description
Summary: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. 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. Our analysis revealed significant differences in the the allelic distribution of variants in different ethnicities. 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.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2017-0101