Report of Confirmation of the rs7853758 and rs885004 Haplotype in SLC28A3

Abstract

Aims: To validate a laboratory-developed test for the nucleoside transporter, SLC28A3, which has been associated with an increased risk of anthracycline-induced cardiomyopathy. Methods: We used Taqman Ò allele discrimination to test for two variants of the SLC28A3 gene: rs7853758 (c.1381C>T) and rs885004 (c.862-360C>T). Results: During the validation process, we noted that several DNA samples obtained from the Coriell Cell Repository (Camden, NJ) were positive for both the c.1381 C > T and c.862-360C>T variants and another variant allele for either c.1381 C > T or c.862-360C>T (e.g., c.1381C>T homozygous/c.862-360C>T heterozygous, c.1381C>T homozygous/c.862-360C>T homozygous). We used de-identified DNA samples from trios of family members (mother, father, and child) to establish that the c.1381 C > T and c.862-360C>T variant alleles could be inherited in cis on the same chromosome. Conclusions: Samples containing three variant alleles suggest that the c.1381 C > T and c.862-360C>T are in cis on the chromosome in some individuals and may have implications when calculating anthracycline-induced cardiomyopathy risk. In this study, we confirm a novel haplotype of SLC28A3 using familial studies.

Association between genetic variants of transmembrane transporters and susceptibility to anthracycline‐induced cardiotoxicity: Current understanding and existing evidence

“…The variant rs885004 in the same transporter has also demonstrated consistent associations with AIC in three internal independent paediatric cohorts, with the minor allele of the variant conferring a decreased AIC risk. 32,33 Of note, both variant alleles of rs7853758 and rs885004 are in strong linkage disequilibrium, 61 while the associations were analysed by separate variant and rarely by haplotype, thus the current data does not allow to precisely assign the observed effects to an individual variant. Intriguingly, although wellreplicated in childhood cancer survivors, the variant rs7853758 is most likely not the causal SNP due to it being synonymous.…”