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2016•Unpublished venueRequires access

Positive TPMT genotype-phenotype correlation underscores importance of TPMT genotyping for personalized thiopurine dosing

Hui‐min Neoh, Mee Lee Looi, Muhiddin Ishak, Mohd Ridhwan Abd Razak, Noor Hamidah Hussin, Zarina Abdul Latiff, Hamidah Alias, Rahman Jamal

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Abstract

This study explored TPMT genotype-phenotype correlation in a group of acute lymphoblastic leukemia (ALL) patients to investigate the potential of TPMT genotyping for personalized thiopurine dosing. Genotyping for G238C (TPMT*2), G460A (TPMT*3B) and A719G (TPMT*3C) loci was determined in 89 subjects via PCR, while TPMT activity was measured using HPLC. TPMT*3C was the only mutant allele detected in 4 heterozygous carriers. These patients had significantly lower (23.0 nmol/g Hb/h) TPMT activity compared to wildtype patients (51.0 nmol/g Hb/h) (p=0.003). Positive correlation between TPMT genotype and phenotype projects the possibility of using TPMT genotyping as a guide prior thiopurine drug administration.

About this research paper

What this paper is about

This study explored TPMT genotype-phenotype correlation in a group of acute lymphoblastic leukemia (ALL) patients to investigate the potential of TPMT genotyping for personalized thiopurine dosing. Genotyping for G238C (TPMT*2), G460A (TPMT*3B) and A719G (TPMT*3C) loci was determined in 89 subjects via PCR, while TPMT activity was measured using HPLC. TPMT*3C was the only mutant allele detected in 4 heterozygous carriers. These patients had significantly lower (23.0 nmol/g Hb/h) TPMT activity compared to wildtype patients (51.0 nmol/g Hb/h) (p=0.003). Positive correlation between TPMT genotype and phenotype projects the possibility of using TPMT genotyping as a guide prior thiopurine drug administration.

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Available abstract

This study explored TPMT genotype-phenotype correlation in a group of acute lymphoblastic leukemia (ALL) patients to investigate the potential of TPMT genotyping for personalized thiopurine dosing. Genotyping for G238C (TPMT*2), G460A (TPMT*3B) and A719G (TPMT*3C) loci was determined in 89 subjects via PCR, while TPMT activity was measured using HPLC. TPMT*3C was the only mutant allele detected in 4 heterozygous carriers. These patients had significantly lower (23.0 nmol/g Hb/h) TPMT activity compared to wildtype patients (51.0 nmol/g Hb/h) (p=0.003). Positive correlation between TPMT genotype and phenotype projects the possibility of using TPMT genotyping as a guide prior thiopurine drug administration.

Key concepts: Thiopurine methyltransferase, Genotyping, Dosing, Genotype, Pharmacogenetics, Phenotype, Genotype-phenotype distinction, Allele

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Positive TPMT genotype-phenotype correlation underscores importance of TPMT genotyping for personalized thiopurine dosing — Research Paper | ScholarLens