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Association of UDP-glucuronosyltransferase 1A9 polymorphisms with adverse reactions to catechol-O-methyltransferase inhibitors in Parkinson’s disease patients

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP-glucuronosyltransferase 1A9 genotypes UGT1A9*1b and UGT1A9*3a, which were previously identified in individual cases of COMT inhibitor-induced toxicity.

Methods

The study included 52 Parkinson’s disease (PD) patients on COMT inhibitors without evidence of adverse reactions and 11 PD patients who had been withdrawn from COMT inhibitors due to adverse reactions. UGT1A9*1b was identified by direct sequencing of the PCR amplification of the gene and UGT1A9*3a was assayed by real-time PCR.

Results

The frequency of the *3a/*3a and *1/*3a genotype variants was 45.5 % in subjects with adverse reactions and 21.1 % in subjects without adverse reactions [overall UGT1A9*3a allele frequency 27.3 vs. 11.5 %, P = 0.087; odds ratio (OR) 2.87, 95 % confidence interval (CI) 0.94–8.77]. The frequency of genotype combinations leading to low glucuronosyltransferase activity (*3a/*3a irrespective of *1b or *1/*3a and *1/*1b) was 5.8 % in subjects without adverse reactions and 36.4 % in subjects with adverse reactions (P = 0.014; OR 9.33, 95 % CI 1.71–50.78).

Conclusions

In PD patients UDP-glucuronosyltransferase 1A9 genotypes are associated with adverse reactions to COMT inhibitors, leading to treatment withdrawal. UDP-glucuronosyltransferase 1A9 genotyping may be a screening and/or diagnostic test to assist individualized treatments with COMT inhibitors.

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Acknowledgments

The collaboration of Dr. Cristina Pianezzola, MD, Dr. Serena Leva, MD, and Dr. Roberta Zangaglia, MD, in clinical data collection and patient monitoring is gratefully acknowledged.

Financial support

The study was supported by a grant from Fondazione Comunitaria del Varesotto Onlus, Varese, Italy (Project no. 146/2008) to MC.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Center for Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9, 21100, Varese, VA, Italy

    Marco Ferrari, Giorgio Bono, Franca Marino & Marco Cosentino

  2. Department of Clinical Medicine, Section of Neurology, University of Insubria, Varese, Italy

    Emilia Martignoni & Giulio Riboldazzi

  3. Interdepartmental Research Center for Parkinson’s Disease, IRCCS Neurological Institute “C. Mondino”, Pavia, Italy

    Fabio Blandini

Authors
  1. Marco Ferrari
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  2. Emilia Martignoni
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  3. Fabio Blandini
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  4. Giulio Riboldazzi
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  5. Giorgio Bono
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  6. Franca Marino
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  7. Marco Cosentino
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Corresponding author

Correspondence to Marco Cosentino.

Additional information

The Authors wish to dedicate this study to the loving memory of Emilia Martignoni, dearest friend, caring physician, and invaluable scientist.

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Ferrari, M., Martignoni, E., Blandini, F. et al. Association of UDP-glucuronosyltransferase 1A9 polymorphisms with adverse reactions to catechol-O-methyltransferase inhibitors in Parkinson’s disease patients. Eur J Clin Pharmacol 68, 1493–1499 (2012). https://doi.org/10.1007/s00228-012-1281-y

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  • DOI: https://doi.org/10.1007/s00228-012-1281-y

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