Genetic variation in dihydropyrimidine dehydrogenase (DPYD) gene in a healthy adult Indian population. (January 2015)

• Record Type: Journal Article
• Authors: Iyer, Sandhya N.; Singhal, Rekha S.; Hegde, Madhuri R.; Ankala, Arunkanth
• Is Part Of: Annals of human biology. Volume 42:Number 1(2015:Jan./Feb.)
• Page Start: 97
• Page End: 100
• Publication Date: 2015-01
• Subjects: Human biology -- Periodicals; 612
• DOI: 10.3109/03014460.2014.942365
• Languages: English
• ISSNs: 0301-4460

Abstract

<abstract> <title>Abstract</title> <p> <italic>Background</italic>: Dihydropyrimidine dehydrogenase (DPD) encoded by <italic>DPYD</italic> gene is the major enzyme involved in metabolism of 5-flurouracil (5-FU), a pyrimidine analogue used in cancer chemotherapy. Although very effective as a cancer therapeutic drug, if not rapidly metabolized, 5-FU may prove lethal. Single nucleotide variants (SNVs) within <italic>DPYD</italic> that modulate DPD enzyme activity contribute to 5-FU toxicity.</p> <p> <italic>Study</italic>: This study looked for <italic>DPYD</italic> SNVs common in the Indian population that might be associated with variable DPD activity and drug toxicity. To achieve this, sequencing analysis was performed of all 23 exons and flanking intronic regions of the <italic>DPYD</italic> gene in a cohort of 50 healthy adult Indians. This study detected 22 SNVs including intronic, synonymous and non-synonymous changes in the <italic>DPYD</italic> gene, of which six have not been documented before. Allelic frequency was calculated for the observed variants and linkage disequilibrium (LD) analysis was performed on variants with frequency ≥0.1 to identify haplotypes.</p> <p> <italic>Conclusions</italic>: This study provides a brief overview of the genetic polymorphism in <italic>DPYD</italic> in Indians and emphasizes the need for a large scale extensive study to establish markers associated with the frequently observed variable drug metabolism.</p> </abstract>