Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 46, Issue 7 (Jul 2008)

Issues

Thiopurine S-methyltransferase (TPMT) pharmacogenetics: three new mutations and haplotype analysis in the Estonian population

Riin Tamm / Kersti Oselin / Kristi Kallassalu
  • 3Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia and Estonian Biocentre, Tartu, Estonia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Reedik Magi / Kaili Anier / Maido Remm / Andres Metspalu
  • 7Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia, Estonian Biocentre, Tartu, Estonia and Estonian Genome Project of University of Tartu, Tartu, Estonia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2008-05-22 | DOI: https://doi.org/10.1515/CCLM.2008.187

Abstract

Background: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme involved in the metabolism of thiopurine drugs. To date, at least 25 single nucleotide polymorphisms have been reported in the TPMT gene, 23 of these are associated with reduced enzyme activity.

Methods: The aim of the present study was to sequence the whole coding region of TPMT (exons 3–10) to identify known and novel TPMT sequence variants amongst healthy Estonians. Erythrocyte TPMT activity was also measured to carry out a genotype-phenotype comparison.

Results: A total of 21 subjects were heterozygous for known TPMT alleles (*2, *3A, *3C, *9, *12). Several other previously described intronic and exon polymorphisms were identified. Three novel mutations were detected −30T>A in exon 3, 10A>G in intron 3, and 145A>G in intron 10. Association analysis revealed four markers (114T>A, 94T>A, 460G>A, 719A>G) whose frequencies were significantly different in intermediate (enzyme activity ≤60 ng/mL/h) methylators compared to normal (enzyme activity 61–139 ng/mL/h) and high (enzyme activity ≥140 ng/mL/h) methylators (p<0.001). Haplotype analysis found one haplotype to be associated with intermediate TPMT activity.

Conclusions: Our results point to several markers that predict reduced enzyme activity. None of the identified markers were associated with high enzyme activity.

Clin Chem Lab Med 2008;46:974–9.

Keywords: enzyme activity; haplotype analysis; pharmacogenetics; thiopurine methyltransferase (TPMT)

About the article

Corresponding author: Riin Tamm, Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia Street, 51010, Tartu, Estonia Phone: +372-737-5881, Fax: +372-742-0286,


Received: 2008-01-08

Accepted: 2008-03-06

Published Online: 2008-05-22

Published in Print: 2008-07-01


Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2008.187.

Export Citation

©2008 by Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Gordon W Moran
World Journal of Gastroenterology, 2015, Volume 21, Number 25, Page 7795
[2]
Vid Mlakar, Patricia Huezo-Diaz Curtis, Chakradhara Satyanarayana Uppugunduri, Maja Krajinovic, and Marc Ansari
International Journal of Molecular Sciences, 2016, Volume 17, Number 9, Page 1502
[3]
Lilla M Roy, Richard M Zur, Elizabeth Uleryk, Chris Carew, Shinya Ito, and Wendy J Ungar
Pharmacogenomics, 2016, Volume 17, Number 6, Page 633
[4]
Salma M. Wakil, Cao Nguyen, Nzioka P. Muiya, Editha Andres, Agnieszka Lykowska-Tarnowska, Batoul Baz, Asma I. Tahir, Brian F. Meyer, Grant Morahan, and Nduna Dzimiri
Disease Markers, 2015, Volume 2015, Page 1
[5]
Hamsa T. Tayeb, Dana H. Bakheet, Khaled Zaza, Salma M. Wakil, and Nduna Dzimiri
Journal of Pharmacy and Pharmacology, 2015, Volume 67, Number 7, Page 972
[6]
Hyun-Young Kim, Soo Hyun Lee, Mi-Na Lee, Jong-Won Kim, Young-Ho Kim, Mi Jin Kim, Yoo Min Lee, Ben Kang, Yon Ho Choe, Na Hee Lee, Dong Hwan Kim, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, and Hong Hoe Koo
Pharmacogenetics and Genomics, 2015, Volume 25, Number 3, Page 143
[7]
Chakradhara Rao S. Uppugunduri and Marc Ansari
European Journal of Clinical Pharmacology, 2012, Volume 68, Number 5, Page 887
[8]
Patchva Dorababu, Shaik Mohammad Naushad, Vijay Kumar Kutala, and Raghunadharao Digumarti
European Journal of Clinical Pharmacology, 2012, Volume 68, Number 5, Page 885
[9]
Gurusamy Umamaheswaran, Dhakchinamoorthi Krishna Kumar, Dhandapani Kayathiri, Subramanian Rajan, Deepak Gopal Shewade, Steven Aibor Dkhar, Sajjanavar Manjunath, Prayaga Ushakiran, Gangadharan Reneega, Kukreti Ritushree, and Chandrasekaran Adithan
Molecular Biology Reports, 2012, Volume 39, Number 5, Page 6343
[10]
Qiping Feng, Suda Vannaprasaht, Yi Peng, Susothorn Angsuthum, Yingyos Avihingsanon, Vivien C. Yee, Wichittra Tassaneeyakul, and Richard M. Weinshilboum
Biochemical Pharmacology, 2010, Volume 79, Number 7, Page 1053
[11]
Salma Melaouhia, Monia Fékih, Anne Garat, Delphine Allorge, Henda Ferchichi, Anis Klouz, Jalel Boubaker, Franck Broly, and Mohamed Lakhal
Clinics and Research in Hepatology and Gastroenterology, 2012, Volume 36, Number 2, Page 178
[12]
Natasa Karas-Kuzelicki, Miha Milek, and Irena Mlinaric-Rascan
Clinical Biochemistry, 2010, Volume 43, Number 1-2, Page 37
[13]
Natasa Karas-Kuzelicki and Irena Mlinaric-Rascan
Pharmacogenomics, 2009, Volume 10, Number 8, Page 1309

Comments (0)

Please log in or register to comment.
Log in