Tracing the origin of the most common thiopurine methyltransferase (TPMT) variants: preliminary data from the patterns of haplotypic association with two CA repeats

Annals of Human Genetics
S AlvesM J Prata

Abstract

Thiopurine methyltransferase (TPMT) is an essential enzyme for normal metabolism of thiopurine drugs. In humans TPMT activity is largely dependent upon genetic variation at the TPMT locus, with TPMT*3A and TPMT*3C being the most frequent mutant alleles associated with reduced activity. TPMT*3C is a widespread allele reaching the highest frequencies in Africans, whereas TPMT*3A is virtually restricted to Caucasian descendent populations. To estimate the time of origin of these two alleles, we analyzed the levels of diversity at two CA repeats flanking the TPMT gene. In accordance to its pattern of geographical distribution, the study of the decay in linkage disequilibrium over time indicated that TPMT*3A was the younger allele. The estimated age was 5700 years, which coincides with the Neolithic, a period characterized by major population expansion that could have been responsible for the spread of TPMT*3A from its place of origin, maybe a western Eurasian population. TPMT*3C was found to have arisen earlier, roughly 14000 years ago, which could explain the worldwide dispersal of TPMT*3C.

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Citations

Dec 3, 2008·European Journal of Clinical Pharmacology·Edna EfratiEli Sprecher
Jun 4, 2010·European Journal of Clinical Pharmacology·Nancy HakoozWilliam Newman
Jun 30, 2012·Journal of Gastroenterology and Hepatology·Rebecca L Roberts, Murray L Barclay
Sep 3, 2013·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Sandeep Kirit DavavalaTarun Gupta
Jun 23, 2006·Journal of Clinical Pharmacy and Therapeutics·R RossinoM Congia
Nov 5, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Anthony M Marinaki, Monica Arenas-Hernandez
Sep 1, 2017·European Journal of Gastroenterology & Hepatology·Constantina CoucoutsiElias A Kouroumalis
May 1, 2008·Personalized Medicine·Rebecca L RobertsMurray L Barclay

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