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Radboud Repository
Article . 2008
Data sources: Radboud Repository
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The Pharmacogenomics Journal
Article . 2007 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
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UGT1A7 polymorphisms in chronic pancreatitis: an example of genotyping pitfalls

Authors: te Morsche, R. H.; Drenth, J. P.; Truninger, K.; Schulz, H. U.; Kage, A.; Landt, O.; Verlaan, M.; +4 Authors

UGT1A7 polymorphisms in chronic pancreatitis: an example of genotyping pitfalls

Abstract

UDP-glucuronosyltransferases (UGT) catalyze the glucuronidation of various compounds and thus inactivate toxic substrates. Genetic variations reducing the activity of UGT1A7 have been associated with various gastrointestinal cancers. Most recently, the UGT1A7*3 allele has been reported as a significant risk factor for pancreatic disorders, but we could not confirm these data. This study focused on the possible causes for the noted discrepancy. UGT1A7 genotypes were assessed in 37 samples, which were previously analyzed for UGT1A7 polymorphisms by others. We determined genotypes by melting curve analysis and by DNA sequencing. Additionally, we produced UGT1A7*1 and *3 constructs with or without a mutation at position - 57 of UGT1A7 and analyzed various combinations of these constructs. In 14/37 samples UGT1A7 genotyping results differed. The discrepancy could be explained by polymerase chain reaction bias owing to an unbalanced allelic amplification which was caused by a -57T>G variant located within the sequence of the chosen primer template in previous studies. Our findings indicate that most of the previously reported genetic associations between UGT1A7 and gastrointestinal cancers are based on primer-dependent genotyping errors.

Keywords

Polymorphism, Genetic, Genotype, Reverse Transcriptase Polymerase Chain Reaction, Temperature, DNA, NCMLS 5: Membrane transport and intracellular motility, UMCN 5.1: Genetic defects of metabolism, IGMD 2: Molecular gastro-enterology and hepatology, Pancreatitis, Chronic, Fluorescence Resonance Energy Transfer, Humans, Cloning, Molecular, Glucuronosyltransferase, Codon, Polymorphism, Restriction Fragment Length, DNA Primers

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    17
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
17
Average
Average
Top 10%
bronze