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UGT1A7 polymorphisms in chronic pancreatitis: an example of genotyping pitfalls

The Pharmacogenomics Journal volume 8, pages 34–41 (2008)Cite this article

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.

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Abbreviations

CP:

chronic pancreatitis

FRET:

fluorescence resonance energy transfer

PCR:

polymerase chain reaction

RFLP:

restriction fragment length polymorphism

UGT:

UDP-glucuronosyltransferases

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Acknowledgements

We thank Volker Keim (Leipzig, Germany) for providing DNA samples and genotyping data of N34S SPINK1 chronic pancreatitis patients. We also thank Mrs Christiane Jechorek (Magdeburg) and Claudia Güldner (Berlin) for their excellent technical assistance. Dr Joost PH Drenth is supported by an NWO-VIDI grant. This study was partly supported by the Deutsche Forschungsgemeinschaft (Wi 2036/1-1 and Wi 2036/2-1), by grants from the Dutch Foundation of Digestive Diseases (MLDS WS00-21) and Sonnenfeld-Stiftung, Berlin, Germany (Witt), and by IGA MZCR 00000064203/6112 to MM

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Radboud University Medical Center Nijmegen, The Netherlands

    R H M te Morsche, J P H Drenth, M Verlaan & J B M J Jansen

  2. Department of Medicine, Division of Gastroenterology, Kantonspital, Aarau, Switzerland

    K Truninger

  3. Department of Surgery, Otto-von-Guericke University, Magdeburg, Germany

    H-U Schulz

  4. Department of Laboratory Medicine and Pathobiochemistry, Charité, Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany

    A Kage

  5. TIB MOLBIOL, Berlin, Germany

    O Landt

  6. Department of Gastroenterology, Charité, Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany

    J Rosendahl & H Witt

  7. Institute of Biology and Medical Genetics – University Hospital Motol and 2nd School of Medicine of Charles University, Prague, Czech Republic

    M Macek Jr

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  1. R H M te Morsche
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  2. J P H Drenth
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  3. K Truninger
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  4. H-U Schulz
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  6. O Landt
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  7. M Verlaan
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  8. J Rosendahl
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  9. M Macek Jr
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  10. J B M J Jansen
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  11. H Witt
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Correspondence to H Witt.

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The authors declare no duality of interest.

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te Morsche, R., Drenth, J., Truninger, K. et al. UGT1A7 polymorphisms in chronic pancreatitis: an example of genotyping pitfalls. Pharmacogenomics J 8, 34–41 (2008). https://doi.org/10.1038/sj.tpj.6500443

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  • DOI: https://doi.org/10.1038/sj.tpj.6500443

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