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

Marco Ferrari, Emilia Martignoni, Fabio Blandini, Giulio Riboldazzi, Giorgio Bono, Franca Marino, Marco Cosentino

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP- glucuronosyltransferase 1A9 genotypes UGT1A91b and UGT1A93a, 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disease (PD) patients on COMT inhibitors without evidence of adverse reactions and 11 PD patients who had been withdrawn from COMT inhibitors due to adverse reactions. UGT1A91b was identified by direct sequencing of the PCR amplification of the gene and UGT1A93a was assayed by real-time PCR. Results: The frequency of the3a/3a and1/3a genotype variants was 45.5 % in subjects with adverse reactions and 21.1 % in subjects without adverse reactions [overall UGT1A93a 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 of1b or1/3a and1/1b) 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.

Original languageEnglish
Pages (from-to)1493-1499
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Volume68
Issue number11
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Parkinson Disease
Genotype
Odds Ratio
Confidence Intervals
Glucuronosyltransferase
Gene Amplification
Routine Diagnostic Tests
Gene Frequency
UDP-glucuronosyltransferase 1A9
Catechol O-Methyltransferase Inhibitors
Real-Time Polymerase Chain Reaction
Polymerase Chain Reaction
Therapeutics

Keywords

  • Adverse reactions
  • Catechol-O-methyltransferase inhibitors
  • Parkinson's disease
  • UGT1A9

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Association of UDP-glucuronosyltransferase 1A9 polymorphisms with adverse reactions to catechol-O-methyltransferase inhibitors in Parkinson's disease patients. / Ferrari, Marco; Martignoni, Emilia; Blandini, Fabio; Riboldazzi, Giulio; Bono, Giorgio; Marino, Franca; Cosentino, Marco.

In: European Journal of Clinical Pharmacology, Vol. 68, No. 11, 11.2012, p. 1493-1499.

Research output: Contribution to journalArticle

Ferrari, Marco ; Martignoni, Emilia ; Blandini, Fabio ; Riboldazzi, Giulio ; Bono, Giorgio ; Marino, Franca ; Cosentino, Marco. / Association of UDP-glucuronosyltransferase 1A9 polymorphisms with adverse reactions to catechol-O-methyltransferase inhibitors in Parkinson's disease patients. In: European Journal of Clinical Pharmacology. 2012 ; Vol. 68, No. 11. pp. 1493-1499.
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abstract = "Purpose: To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP- glucuronosyltransferase 1A9 genotypes UGT1A91b and UGT1A93a, 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. UGT1A91b was identified by direct sequencing of the PCR amplification of the gene and UGT1A93a was assayed by real-time PCR. Results: The frequency of the3a/3a and1/3a genotype variants was 45.5 {\%} in subjects with adverse reactions and 21.1 {\%} in subjects without adverse reactions [overall UGT1A93a 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 of1b or1/3a and1/1b) 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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AU - Ferrari, Marco

AU - Martignoni, Emilia

AU - Blandini, Fabio

AU - Riboldazzi, Giulio

AU - Bono, Giorgio

AU - Marino, Franca

AU - Cosentino, Marco

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N2 - Purpose: To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP- glucuronosyltransferase 1A9 genotypes UGT1A91b and UGT1A93a, 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. UGT1A91b was identified by direct sequencing of the PCR amplification of the gene and UGT1A93a was assayed by real-time PCR. Results: The frequency of the3a/3a and1/3a genotype variants was 45.5 % in subjects with adverse reactions and 21.1 % in subjects without adverse reactions [overall UGT1A93a 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 of1b or1/3a and1/1b) 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.

AB - Purpose: To investigate the association between adverse reactions to catechol-O-methyltransferase (COMT) inhibitors and the UDP- glucuronosyltransferase 1A9 genotypes UGT1A91b and UGT1A93a, 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. UGT1A91b was identified by direct sequencing of the PCR amplification of the gene and UGT1A93a was assayed by real-time PCR. Results: The frequency of the3a/3a and1/3a genotype variants was 45.5 % in subjects with adverse reactions and 21.1 % in subjects without adverse reactions [overall UGT1A93a 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 of1b or1/3a and1/1b) 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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