Naslov
DPYD haplotype structure for variants *2A, *13, c.2846A>T, c.1236G>A/HapB3, c.496A>G (rs2297595), *6 (rs1801160) and *9A (rs1801265) in the Croatian population

Autori
Ganoci, L. ; Lešnjaković, L. ; Šimičević, L. ; Palić, J. ; Mucalo, I. ; Božina, N.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
European Human Genetics Conference ; Hybrid Conference

Mjesto i datum
Glasgow, Ujedinjeno Kraljevstvo, 10.06.2023. - 13.06.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
DPYD, haplotype, genes

Sažetak
Background: Dihydropyrimidine dehydrogenase, coded by the DPYDgene, isarate-limitingenzyme in the metabolism of fluoropyrimidines.Data on the frequency of DPYD haplo type sand impact of common DPYD variants on fluoropyrimidine-related toxicityis limited.We analysed genotype and haplotype frequencies off our DPYD variants from pharmacogenomics guideline sand three additional common DPYD polymorphisms in the Croatian population. Methods: In this study, we analysed data DPYD genotyping from routine pharmacogenetic testing in cancer patients treated with fluoropyrimidine therapy. A total of 998 subjects of Caucasian an cestry were genotyped for DPYD*2A (c.1905+1G>A), *13 (c.1679T>G), c.2846A>T, c.1236G>A/HapB3, c.496A>G (rs2297595), *6(c.2194G>A, rs1801160) and *9A(c.85T>C, rs1801265)by TaqMan real-time PCR. Genotyping data were analysed to estimate allele frequencies, common haplotypes and haplotype frequencies. Results: The DPYD variants allele frequency were*2A q=0.01653, *13q=0.0005, c.2846A>T q=0.00401, c.1236G>A q=0.02555, *6q=0.05962, *9Aq=0.23447 andc.496A>Gq=0.13176.439subjects (44.0%) were carriers of wt alleles, 141(14.1%) were carriers ofc.496G/*9A genotype, 134 (13.4%) of *1/*9A genotype, 67 (6.7%) of *1/*6 genotype, 36(3.6%) of *1/c.496G genotype, 29(2.9%) ofc.1236A/*9A genotype, 6(0.6%) of *1/c.1236Agenotype.Analysing the combination of DPYD variants revealed that263subjects(26.4%)were carriers of one variant allele, while271(27.2%)were carriers of two or more different (compound) variant alleles. Conclusions: This study provides information on DPYD haplotype frequencies in the Caucasian population, which is essential for the design of pharmacogenetic studies investigating the impact of common DPYD variants and haplotypes on fluoropyrimidine-related toxicity.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA