Investigation of Ivs14+1G>A Polymorphism of Dpyd Gene in a Group of Bosnian Patients Treated with 5-Fluorouracil and Capecitabine

Abstract

Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14 + 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation.

Effectiveness and safety of reduced‐dose fluoropyrimidine therapy in patients carrying the DPYD*2A variant: A matched pair analysis

“…For the literature control cohort, used for comparison of toxicity, a total of 17 published studies were selected, describing clinical data on 86 DPYD *2A variant allele carriers . Patient characteristics of the historical cohort are included in Table .…”

Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups

“…Previous studies have shown that the enzyme deficiency state of the 5-FU degradation pathway causes damage and degeneration of the central nervous system (8, 14, 16). Thus DPYD is known as a biomarker of severe toxicity in chemotherapeutic agents.…”

“…Several genetic variations have been reported in previous studies. DPYD * 2A (rs3918290), located in the intron site, plays the role of an alternative splicing variant, and other polymorphisms such as DPYD * 9A ( rs1801265 ), DPYD * 7 (rs72549309), DPYD * 8 (rs1801266), DPYD * 9B (rs1801267), and DPYD * 10 (rs1801268), affect DPYD enzyme activity in other ways (8-14). …”

TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation genes in Mexican colorectal cancer patients

“…DPD-deficient patients exhibit a normal phenotype until administered with 5-FU or capecitabine. It has been estimated that nearly 3-5% of the general population has the DPD activity below normal (Cerić et al, 2010).…”