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® 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.
Keywords: SLC28A3; haplotype; pharmacogenetics; rs7853758; rs885004.