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

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Alves, S (Author) Other; Rocha, J (Author) FCUP; Amorim, A (Author) FCUP; Prata, MJ (Author) FCUP

Journal

Title: Annals of Human Genetics

Vol. 68

Pages: 313-323

ISSN: 0003-4800

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 21 Citations

Scientific classification

FOS: Natural sciences > Earth and related Environmental sciences

Other information

Authenticus ID: P-000-9GK

DOI: 10.1046/j.1529-8817.2004.00104.x

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11