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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 &amp; 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, r 2  = 1, p &lt; 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.

pharmacogenomics

Novel motif of variable number of tandem repeats in <i>TPMT</i> promoter region and evolutionary association of variable number of tandem repeats with <i>TPMT*3</i> alleles

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

Novel motif of variable number of tandem repeats in TPMT promoter region and evolutionary association of variable number of tandem repeats with TPMT3* alleles