Novel motif of variable number of tandem repeats in TPMT promoter region and evolutionary association of variable number of tandem repeats with TPMT∗3 alleles

Dunja Urbančič, Alenka Šmid, Gabriele Stocco, Giuliana Decorti, Irena Mlinarič-Raščan, Nataša Karas Kuželički

Research output: Contribution to journalArticle

Abstract

Aim: SNPs in the gene for TPMT exemplify one of the most successful translations of pharmacogenomics into clinical practice. This study explains the correlation between common SNPs and variable number of tandem repeats (VNTR) in promoter of the gene. Materials & methods: We determined VNTR polymorphisms, as well as TPMT∗2 and TPMT∗3 SNPs and TPMT activity in Slovenian and Italian individuals and lymphoblastoid cell lines. Results: We observed a previously unreported VNTR allele, AB7C, in a TPMT∗3A heterozygous individual. VNTRs with two (AB2C) and three or more (ABnC, n ≥ 3) B motifs were statistically significant in complete linkage disequilibrium (D′ = 1, r2 = 1, p < 0.0001) with the TPMT∗3C and TPMT∗3A alleles, respectively. Conclusion: The study provides insights into the stepwise evolution of TPMT∗3 alleles from ∗3C to ∗3A, with increasing number of B motifs in the VNTR region.

Original languageEnglish
Pages (from-to)1311-1322
Number of pages12
JournalPharmacogenomics
Volume19
Issue number17
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • acute lymphoblastic leukemia
  • genetic polymorphisms
  • inflammatory bowel disease
  • linkage disequilibrium
  • lymphoblastoid cell lines
  • thiopurine S-methyltransferase
  • TPMT
  • TPMT activity
  • variable number of tandem repeats
  • VNTR

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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