Journal article
Thiopurine methyltransferase pharmacogenetics : cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1
Drug metabolism and disposition, Vol.23(3), pp.398-405
1995
DOI: 10.1016/S0090-9556(25)06551-1
PMID: 7628307
Abstract
Thiopurine methyltransferase (TPMT) is a genetically polymorphic enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. This genetic polymorphism is an important factor responsible for individual variation in thiopurine drug response. A cDNA for TPMT has been cloned from T84 human colon carcinoma cells. Northern blot analysis of multiple human tissues was performed with the T84 human colon carcinoma TPMT cDNA open reading frame (ORF) as a probe as one step toward understanding the molecular basis for the TPMT genetic polymorphism. Three mRNA species (approximately 1.4, 2.0, and 3.6 kb in length) were present in all tissues studied, including liver. However, none of these mRNAs matched the length of the 2.7 kb T84 TPMT cDNA. Therefore, it was important to clone a TPMT cDNA from a human drug-metabolizing organ such as the liver to determine whether its sequence matched that of the cDNA cloned from the T84 cell line. A human liver cDNA library was screened with the T84 TPMT cDNA ORF as a probe, and a 1.8 kb cDNA was isolated with a coding region sequence identical to that of the T84 TPMT cDNA. The TPMT cDNA ORF was then used to screen a human lymphocytes genomic DNA library in an attempt to clone the TPMT gene(s) in humans. Three intronless clones were isolated with identical ORF sequences that were 96% identical to that of the TPMT cDNA, but which contained multiple nucleotide substitutions and one deletion. The 3'- and 5'-flanking regions of one of the genomic DNA clones were sequenced.
Details
- Title: Subtitle
- Thiopurine methyltransferase pharmacogenetics : cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1
- Creators
- Daniel Lee - Mayo ClinicCarol Szumlanski - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United StatesJon Houtman - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United StatesRonald Honchel - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United StatesKatherine Rojas - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United StatesJoan Overhauser - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United StatesEric D Wieben - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United StatesRichard M Weinshilboum - Mayo medical school/Mayo clin./Mayo foundation, dep. pharmacology, Rochester MN 55905-0001, United States
- Resource Type
- Journal article
- Publication Details
- Drug metabolism and disposition, Vol.23(3), pp.398-405
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1016/S0090-9556(25)06551-1
- PMID
- 7628307
- ISSN
- 0090-9556
- eISSN
- 1521-009X
- Language
- English
- Date published
- 1995
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984094673602771
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